Abstract Background: Breast cancer (BC) is the commonest diagnosed cancer in Singaporean women. Increasingly, non-metastatic BC are treated aggressively with neoadjuvant therapy (NAT). Early identification and addressing supportive care needs of NAT treated patients is important for effective cancer care whilst maintaining optimal physical, psychological and social function. This project aims to explore the longitudinal trends of quality of life (QOL) of BC patients enrolled in a NAT program. Methods: This was a prospective cohort study of females aged 21 diagnosed with non-metastatic BC, referred to the NAT program at the SingHealth network of acute hospitals. The Functional Assessment of Cancer Therapy-Breast (FACT-B) was used as a health related QOL measure prior to NAT, within 2 months post definitive breast surgery and at 1-year post diagnosis. In older adults (OA) ≥65 years, the Attitude scale, Now vs Later as well as Health Outcome tool were also performed at baseline. Here we report pre-NAT baseline FACT-B and questionnaire results of OA patients recruited into the NAT program between Jun 2020 and Jun 2021. Results: Pre-NAT median FACT-B scores was 117 (IQR 102-126) for the entire cohort (n=119) and 116 (IQR 104-126) for OA (n=22). OA had significantly lower median Social Wellbeing score at baseline compared to patients < 65 years (p=0.01), while Physical, Emotional, and Functional Wellbeing were not significantly different. More than 50% of OA favoured QOL over quantity of life on the Attitude Scale. 68% of patients would rather have QOL now than 1 year later with half expecting their QOL to reduce by 50% in this time period. When the time scale was extended to 5 years, 64% would rather have QOL 5-years from now instead of QOL now with close to 80% expecting their QOL to be lower in 5 years than presently. Of the 4 outcomes, maintaining independence scored the highest, followed by keeping alive, then reducing/eliminating pain and other symptoms. Conclusion: Our study suggests that OA with BC report similar QOL to younger patients at baseline prior to NAT. Majority of OA patients favoured QOL over quantity of life, and viewed the ability to maintain independence as more important than survival prolongation representing their unique attitude towards cancer treatment and outcomes. Citation Format: Jun Ma, Zewen Zhang, Jasmine Yun Ting Tan, Whee Sze Ong, Sulastri Kamis, Benita Kiat Tee Tan, Veronique Kiak Mien Tan, Ravindran Kanesvaran, Tira Jing Ying Tan. Quality of Life and Perspectives of Older Adults with Early & Locally Advanced Breast Cancers Undergoing Pre-operative Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-21.
Cell state transitions control the functional behavior of cancer cells. Epithelial-to-mesenchymal transition (EMT) confers cancer stem cell-like properties, enhanced tumorigenicity and drug resistance to tumor cells, while mesenchymal-epithelial transition (MET) reverses these phenotypes. Using high-throughput chemical library screens, retinoids are found to be potent promoters of MET that inhibit tumorigenicity in basal-like breast cancer. Cell state transitions are defined by reprogramming of lipid metabolism. Retinoids bind cognate nuclear receptors, which target lipid metabolism genes, thereby redirecting fatty acids for β-oxidation in the mesenchymal cell state towards lipid storage in the epithelial cell state. Disruptions of key metabolic enzymes mediating this flux inhibit MET. Conversely, perturbations to fatty acid oxidation (FAO) rechannel fatty acid flux and promote a more epithelial cell phenotype, blocking EMT-driven breast cancer metastasis in animal models. FAO impinges on the epigenetic control of EMT through acetyl-CoA-dependent regulation of histone acetylation on EMT genes, thus determining cell states.
Separation of lipoproteins by traditional sequential salt density floatation is a prolonged process ( approximately 72 h) with variable recovery, whereas iodixanol-based, self-generating density gradients provide a rapid ( approximately 4 h) alternative. A novel, three-layered iodixanol gradient was evaluated for its ability to separate lipoprotein fractions in 63 subjects with varying degrees of dyslipidemia. Lipoprotein cholesterol, triglycerides, and apolipoproteins were measured in 21 successive iodixanol density fractions. Iodixanol fractionation was compared with sequential floatation ultracentrifugation. Iodixanol gradient formation showed a coefficient of variation of 0.29% and total lipid recovery from the gradient of 95.4% for cholesterol and 84.7% for triglyceride. Recoveries for VLDL-, LDL-, and HDL-cholesterol, triglycerides, and apolipoproteins were approximately 10% higher with iodixanol compared with sequential floatation. The iodixanol gradient effectively discriminated classic lipoproteins and their subfractions, and there was evidence for improved resolution of lipoproteins with the iodixanol gradient. LDL particles subfractionated by the gradient showed good correlation between density and particle size with small, dense LDL (<25.5 nm) separated in fractions with density >1.028 g/dl. The new iodixanol density gradient enabled rapid separation with improved resolution and recovery of all lipoproteins and their subfractions, providing important information with regard to LDL phenotype from a single centrifugation step with minimal in-vitro modification of lipoproteins.
Abstract Background: Non-metastatic breast cancers (BC) are increasing treated with neoadjuvant therapy (NAT). Complete pathological response (pCR) is associated with improved survival. Early identification of care needs during NAT is crucial. We report our institution’s experience with NAT. Methods: A prospectively recruited cohort diagnosed with BC, referred to NAT program at SingHealth acute hospitals between June 2020 and June 2021. Demographics, clinical data, pCR (absence of invasive carcinoma in breast and axilla), and Functional Assessment of Cancer Therapy Breast (FACT-B) as quality of life (QOL) measure were collected. Definition of young BC (YBC) were ≤40 years, older adults (OA) ≥65 years. Results: Among 119 eligible patients, 7 (6%) were clinically stage 1, 71 (60%) stage 2, and 41 (35%) stage 3. Twenty-eight (24%) were triple negative (TNBC; defined as HER2- hormonal receptor 0-10% [HR-]), 26 (22%) HER2+ HR-, 45 (38%) HER2+ HR+, 20 (17%) HER2- HR+. Among 71 HER2+ BC, two-thirds received anthracycline (A) based chemotherapy, a quarter A-sparing and remaining 9% taxane only. Majority (89%) received dual HER2 blockade. Among TNBC, 28 (71%) received additional platinum and 2 (7%) immunotherapy. Majority (77%; n=92) completed NAT. Toxicity was main reason for incompletion. Three patients did not undergo surgery: 1 defaulted, 1 demised and the last patient’s surgery was not due at analysis. Of the 116 who underwent surgery, 23 (20%) had breast conservation and 93 (80%) mastectomy. Forty-nine (42%) achieved pCR - 12 (43%) TNBC, 17 (65%) HER2+ HR-, 20 (44%) HER2+ HR+ and 0 in HER2- HR+ (p < 0.001). The pCR rates were also lower by increasing age (Multivariable OR 0.93; 95% CI, 0.90-0.97). Baseline median FACT-B scores was 117 (IQR 102-126) for the cohort: 108 for YBC, 116 for OA and 120 for the rest (p=0.200). At baseline, median score was 28, 24, 18, 22 and 27 in physical, social, emotional, functional wellbeing and BC subscale, respectively, and YBC and OA patients had lower social wellbeing scores than the remaining cohort (22 vs 24, p=0.011). Conclusion: Highest pCR were observed with HER2+ followed by TNBC. Pre-operatively, FACT-B scores were comparable by demographics, staging and tumor subtypes. However, care must be paid to social wellbeing for women in age extremes undergoing NAT. Citation Format: Zewen Zhang, Jun Ma, Jasmine Yun Ting Tan, Whee Sze Ong, Sulastri Kamis, Grace Yang, Benita Kiat Tee Tan, Veronique Kiak Mien Tan, Tira J. Tan. Neoadjuvant therapy in Asian breast cancer patients with early & locally advanced breast cancers – A contemporary experience from a large tertiary hospital in Singapore [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-49.
Background Geriatric assessment (GA) has been shown to be pivotal to the prognosis of elderly cancer patients. A G8 screening tool could act as a potential surrogate to identify patients who would benefit from further GA in a busy oncology clinic and a digital version would allow for a wider application. Objectives To develop a digital self-reported version of G8, and to compare its outcomes with in-person G8 administered by a healthcare professional. Methods A total of 483 cancer patients aged 70 years and older who received an in-person G8 assessment at the National Cancer Centre Singapore (NCCS) clinic, and another 544 who completed the digital self-reported G8 were analysed. Total G8 score ≤14 was defined as positive screen. Results Response rate of the digital self-reported G8 was 50%. Median G8 total score was lower among online screeners than in-person screeners (11 vs 12.5, p < 0.001). The odds of a G8 positive screen among online screeners was higher than that of in-person screeners on multivariable logistic regression analysis (odds ratio = 1.56, 95% CI 1.08-2.26). Some 20 in-person screeners had also completed the digital self-reported G8, and the agreement between their in-person and online G8 total scores was high (concordance correlation coefficient = 0.798, 95% CI 0.635-0.962). Conclusions A digital self-reported G8 is feasible. However, given the higher positive screen rate among the online screeners, replacement of the in-person G8 with the digital self-reported G8 should be implemented only after more conclusive evidence on the agreement between in-person and online G8 score is available.
Abstract Advances in adjuvant therapy have led to increased survival rates after cancer prognosis. Herceptin, a targeted therapy, had first been introduced to Singapore in 2006. We aimed to assess whether subsidies for Herceptin from 2012 will lead to changes in uptake among Human Epidermal Growth Factor Receptor 2 (HER2) positive patients by socio-economic groups. Two-level random-intercept logistic regression was used to model diagnostic test and Herceptin uptake using the Singapore Breast Cancer Cohort from 2006 to 2018, adjusting for covariates such as education, housing type and marital status before and after subsidies. Interrupted time series (ITS) analysis was used to evaluate the impact of Herceptin subsidy on treatment uptake. The concentration index was also computed to measure inequality in uptake by ethnicity and education. We found that the odds of diagnostic testing were not associated with socioeconomic factors. However, before subsidies, the highest education attained (OR = 4.57, 95% CI= (1.90, 11.02), P< 0.01) significantly increased the odds of Herceptin uptake. These odds were levelled after the introduction of subsidies to Herceptin treatment in 2012. After subsidy, we also found that Herceptin uptake increased significantly by 11.4% (95% CI= (3.47%, 19.4%), P=0.016). Also, inequality of Herceptin use decreased especially amongst the Indians, where at least 40% were used in the higher educated group prior to the subsidy. Subsidies have lowered the barriers to Herceptin uptake for marginalized individuals. Having targeted subsidies for socio-economically disadvantaged groups may work more efficiently in providing ease of access than a blanket subsidy in Herceptin.
Abstract Candida endophthalmitis is a serious complication of candidemia. Diagnosis requires identification of ocular lesions on dilated fundoscopy, aided by isolation of the organism from blood and/or vitreous humor. However, the initial ophthalmological examination may be negative in some cases. Experience with isavuconazole for the treatment of Candida endophthalmitis is limited. We present a case of a 65-year-old woman with metastatic breast cancer on chemotherapy who developed Candida dubliniensis endophthalmitis with initial negative ophthalmological examination. She was treated with vitrectomy and 6 weeks of oral fluconazole. Despite vitrectomy and culture-directed antifungal treatment, management was complicated by lack of response to fluconazole and intolerance to other antifungals, necessitating the use of isavuconazole, which proved efficacious.
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