Breast Cancer Patients In Singapore Research Articles

Cost-effectiveness analysis of add-on pertuzumab to trastuzumab biosimilar and chemotherapy as neoadjuvant treatment for human epidermal growth receptor 2-positive early breast cancer patients in Singapore

ABSTRACT Objectives The Asian PEONY trial showed that add-on pertuzumab to trastuzumab and chemotherapy significantly improved pathological complete response in the neoadjuvant treatment of patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC). This study evaluated the cost-effectiveness of pertuzumab as an add-on therapy to trastuzumab and chemotherapy for neoadjuvant treatment of patients with HER2+ EBC in Singapore. Methods A six-state Markov model was developed from the Singapore healthcare system perspective, with a lifetime time horizon. Model outputs were: costs; life-years (LYs); quality-adjusted LYs (QALYs); incremental cost-effectiveness ratios (ICERs). Sensitivity/scenario analyses explored model uncertainties. Results The base case projected the addition of pertuzumab to be associated with improved outcomes by 0.277 LYs and 0.271 QALYs, increased costs by S$1,387, and an ICER of S$5,121/QALY. The ICER was most sensitive to the pCR rate, and the probabilistic sensitivity analysis showed that add-on pertuzumab had an 81.3% probability of being cost-effective at a willingness-to-pay threshold of S$45,000/QALY gained. Conclusions This model demonstrated that the long-term clinical impact of early pertuzumab use, particularly the avoidance of metastatic disease and thus avoidance of higher costs and mortality rates, make neoadjuvant pertuzumab a cost-effective option in the management of patients with HER2+ breast cancer in Singapore.

Effects of housing value and medical subsidy on treatment and outcomes of breast cancer patients in Singapore: A retrospective cohort study

BackgroundSocioeconomic status (SES) is likely to affect survival in breast cancer patients. Housing value is a reasonable surrogate for SES in Singapore where most residents own their own homes, which could be public (subsidised) or private housing. We evaluated effects of housing value and enhanced medical subsidies on patients’ presentation, treatment choices, compliance and survival in a setting of good access to healthcare. MethodsA retrospective analysis of breast cancer patients treated in a tertiary hospital cluster from 2000 to 2016 was performed. Individual-level Housing value Index (HI) was derived from each patient's address and then grouped into 3 tiers: HI(high)(minimal subsidy), HI(med)(medium subsidy) and HI(low)(high subsidy). Cox regression was performed to evaluate the associations between overall survival (OS) and cancer-specific survival (CSS) with HI and various factors. FindingsWe studied a multiracial cohort of 15,532 Stage 0–IV breast cancer patients. Median age was 53.7 years and median follow-up was 7.7 years. Patients with lower HI presented with more advanced disease and had lower treatment compliance. On multivariable analysis, compared to HI(high) patients, HI(med) patients had decreased OS (HR=1.14, 95% CI 1.05–1.23) and CSS (HR=1.15, 95% CI 1.03–1.27), and HI(low) patients demonstrated reduced OS (HR=1.16, 95% CI 1.01–1.33). Ten-year non-cancer mortality was higher in lower HI-strata. Enhanced medical subsidy approximately halved treatment noncompliance rates but its receipt was not an independent prognostic factor for survival. InterpretationDespite good healthcare access, lower-HI patients have poorer survival from both cancer and non-cancer causes, possibly due to delayed health-seeking and poorer treatment compliance. Enhanced subsidies may mitigate socioeconomic disadvantages. FundingNone.

Under-Treatment and Poorer Survival Outcomes in Elderly Breast Cancer Patients in Singapore: A Comparison with Younger Patients in a Tertiary Institution

Introduction: The numbers of elderly patients with breast cancers are increasing with an ageing population, yet clinical research on these patients is still lacking. This study aims to examine the differences between elderly patients and their younger counterparts, with a view to optimize management plans for the former. Methods: Patients ≥ 40 years old with histologically proven breast cancer between 1991 and 2008 were identified from our database, and grouped according to age for analyses: old elderly (≥75 years), young elderly (65 to 74 years) and young (40 to 64 years). Clinicopathologic characteristics, treatment and survival rates were compared across the 3 groups. Results: There were 103 (11.53%) old elderly, 147 (16.5%) young elderly and 643 (72.0%) young patients. The 2 elderly groups presented at later stages, received less adjuvant or palliative chemotherapy (P < 0.001), and less adjuvant radiotherapy (P < 0.001), compared to the younger patients. Both breast cancer specific survival (CSS) and overall survival (OS) in the old elderly (CSS: 64.7% (95% confidence interval [CI]: 53.4% - 73.8%), OS: 46.4% (95% CI: 35.6% - 56.4%)) and young elderly group (CSS: 82.4% (95% CI: 74.4% - 88.0%) OS: 78.6% (95% CI: 70.4% - 84.8%)) were lower than the young patient group (CSS: 84.9% (95% CI: 81.6% - 87.7%), OS: 83.4% (95% CI: 80.0% - 86.3%)) at 5 years. Conclusion: Our findings showed that clinicopathologic characteristics of elderly breast cancer patients differed from their younger counterparts. Poorer survival outcomes among our elderly patients may be the result of their under-treatment.

Prevalence and determinants of adherence to oral adjuvant endocrine therapy among breast cancer patients in Singapore

Objective:The success of oral adjuvant endocrine therapy (OAET) is greatly influenced by patients’ level of adherence to treatment. The objective of this study is to measure the prevalence and determinants of adherence to OAET among breast cancer patients in Singapore.Methods:A cross-sectional survey of patients supplemented by analysis of their prescription records was used to collect data. Adherence to OAET was assessed using the Morisky Medication Adherence Scale-4 items and evaluation of refill gaps. Univariate and multivariate analyses were done to evaluate the association between patients’ characteristics and adherence to OAET.Results:A total of 157 women who have started OAET at least 6 months before the time of interview participated in the study, of which less than half (64 patients, 40.8%) of the patients had high adherence. Univariate analysis identified patients who were 57 years or older (P = 0.027), unemployed (P = 0.027), on aromatase inhibitors (P = 0.023), on three or more concurrent medications (P = 0.001), and had one or more comorbidities (P = 0.000) to be significantly more adherent. However, only the number of comorbidities was found to be an independent predictor of adherence in a multiple logistic regression analysis (adjusted odds ratio = 2.60; 95% confidence interval = 1.208–5.593; P = 0.015). Forgetfulness was the main reason for nonadherence mentioned by 63 (67.7%) of the 93 nonadherent patients.Conclusions:Low level of OAET adherence was found in this study, and forgetfulness was cited as the main reason for nonadherence. Patients were generally receptive to the implementation of various strategies to assist them with their medication-taking behavior

Method Development for Detection of E545A Mutation PIK3CA Gene in Breast Cancer Patients Using Tm Shift SYBR Green I qPCR

E545A is one of the point mutations, and its frequency is high in PIK3CA gene (3.8%), particularly breast cancer patients in Singapore (13.8%) and Mexico (11.5%). In addition to induce breast cancer, the mutation also caused resistance of anti-HER2 in HER2 cancer subtype. The tremendous effect of this mutation was not supported by affordable detection method. This study aimed to develop a feasible and sensitive method of E545A detection. The developing method used Tm and Ct to identify samples. Based on optimization, the best condition was obtained at optimization 2 at annealing temperature of 65°C. At this condition, Tm and Ct of each sample were (a) exon 9 (78.4°C and 13.005±0.007) and (b) E5454A (80.4°C and 10.07±0.1). This method also demonstrated good precision as observed in variance coefficient of intra and inter assay (0). Thus, method for E5454A detection mutation was successfully developed.

A culturally adapted survivorship programme for Asian early stage breast cancer patients in Singapore: A randomized, controlled trial.

As cancer mortality rates improve in Singapore, there is an increasing need to improve the transition to posttreatment survivorship care. This study aimed to evaluate the effectiveness of a psychoeducation group (PEG) intervention program compared with usual care to reduce distress for physical symptom and psychological aspects in Asian breast cancer survivors who have completed adjuvant chemotherapy. This was a randomized, controlled trial comprising 72 Asian early stage breast cancer survivors who were randomized into the PEG (n=34) or the control (n=38) arm. The participants in the PEG arm underwent a weekly multidisciplinary PEG program delivered in a group format over 3weeks coupled with cultural adaptation. Both arms were assessed at baseline and 2months after intervention using the Rotterdam Symptom Checklist, Beck Anxiety Inventory, and EORTC QLQ-C30. A satisfaction questionnaire was also conducted among those survivors who have participated in the PEG program. Effective sizes were calculated using Cohen d. The mean age±SD of all participants was 53.0±8.9years, with the majority being Chinese (84.7%) and Malay (6.9%), and clinical characteristics were well balanced in both arms. Compared to the control arm, the PEG arm showed a significantly greater reduction in physical symptom distress (d=0.76, P=.01) and fatigue (d=0.49, P=.04). The 82.4% of the participants in the intervention group responded to the satisfaction questionnaire, and the majority (92.9%) agreed that the overall duration of the PEG intervention program was appropriate. A culturally adapted PEG program was effective in reducing physical symptom distress in Asian breast cancer survivors. (ClinicalTrials.gov: NCT02600299).

Psychometric properties and measurement equivalence of the English and Chinese versions of the Beck Anxiety Inventory in patients with breast cancer.

There is a lack of psychometric data for both the English and Chinese versions of Beck Anxiety Inventory (BAI) to support its usage among breast cancer patients. This study examined the psychometric properties and measurement equivalence of the English and Chinese versions of BAI among breast cancer patients in Singapore. Patients were recruited from two major cancer centers in Singapore. The criterion and construct validity of BAI was assessed by its correlation strength with (1) the emotional functioning subdomain of EORTC QLQ-C30 and (2) constructs related to anxiety, namely fatigue, dyspnea, and quality of life. The known-group validity was assessed according to the patients' breast cancer stage, religious beliefs, and emotional functioning levels. The internal consistency of the BAI domains was evaluated using Cronbach's alpha coefficient. Regression analysis was performed to compare the BAI total and domain scores between the two language versions. Data from 244 patients (144 English-speaking and 100 Chinese-speaking) were analyzed. For both language versions, the BAI total scores correlated moderately with the EORTC QLQ-C30 emotional functioning subdomain (r=-0.655 and -0.601). Correlations with fatigue, quality of life, and dyspnea were moderate (|r|=0.456-0.606). Patients with poorer emotional functioning reported higher anxiety levels, establishing known-group validity. All BAI domains demonstrated satisfactory internal consistencies (α=0.74-0.87), except for the panic domain (α=0.57-0.61). Possible measurement equivalence between the language versions was established. Both English and Chinese versions of BAI are valid, reliable, and possibly equivalent for future use.

Mapping the functional assessment of cancer therapy-breast (FACT-B) to the 5-level EuroQoL Group's 5-dimension questionnaire (EQ-5D-5L) utility index in a multi-ethnic Asian population.

PurposeTo develop an algorithm for mapping the Functional Assessment of Cancer Therapy – Breast (FACT-B) to the 5-level EuroQoL Group’s 5-dimension questionnaire (EQ-5D-5L) utility index.MethodsA survey of 238 breast cancer patients in Singapore was conducted. Models using various regression methods with or without recognizing the upper boundary of utility values at 1 were fitted to predict the EQ-5D-5L utility index based on the five subscale scores of the FACT-B. Data from a follow-up survey of these patients were used to validate the results.ResultsA model that maps the physical, emotional, functional well-being and the breast cancer concerns subscales of the FACT-B to the EQ-5D-5L utility index was derived. The social well-being subscale was not associated to the utility index. Although theoretical assumptions may not be valid, ordinary least square outperformed other regression methods. The mean predicted utility index within each performance status level at follow-up deviated from the observed mean less than the minimally important difference of EQ-5D for cancer patients.ConclusionsThe mapping algorithm converts the FACT-B to the EQ-5D utility index. This enables oncologists, clinical researchers and policy makers to obtain a quantitative utility summary of a patient’s health status when only the FACT-B is assessed.

Patient-reported outcomes are associated with patient-oncologist agreement of performance status in a multi-ethnic Asian population.

This study aims to compare the performance status assessed by breast cancer patients and their oncologist and investigate the factors associated with the patient-oncologist disagreement in a multi-ethnic Asian population. This is a cross-sectional study of 270 female breast cancer patients in Singapore. Patients' performance status was rated by the patients and their treating oncologists. Patients were also asked to complete two instruments regarding their health status and health-related quality of life. The proportions of patients with assessment of performance status the same as and different from their oncologist were calculated. The level of agreement was quantified by Kappa statistics together with the confidence interval (CI). Multinomial logistic regression analyses were performed to examine potential factors associated with the patient-oncologist disagreement. Approximately half (136/270) of the patients agreed with the oncologist in assessing performance status. Among the disagreeing half, 48 (17.8 %) patients rated better and 86 (31.9 %) poorer than the oncologists. The unweighted and quadratic-weighted Kappa statistics were, respectively, 0.21 (95 % CI = 0.13 to 0.29) and 0.34 (95 % CI = 0.26 to 0.42). Multivariable multinomial logistic regressions showed that outpatient, language used, and evidence of disease were associated with patients' better assessment than the oncologists, while age, physical well-being, and pain/discomfort were associated with patients' poorer assessment. The patient-oncologist agreement was weak to moderate. When discrepant, patients tended to rate themselves worse than the oncologists assessed. Poorer assessment rated by patients was associated with their physical well-being. Patients who self-rated poorer may require further evaluation of any unobserved symptoms.

Validation of EORTC QLQ-C30 and QLQ-BR23 questionnaires in the measurement of quality of life of breast cancer patients in Singapore

Objective:To validate EORTC QLQ-C30 and EORTC QLQ-BR23 questionnaires and to measure the health-related quality of life (HRQOL) of women with breast cancer in Singapore during their first 4 years of post-diagnosis and treatments.Methods:A quantitative and cross-descriptive sectional study. All of 170 subjects were recruited in a Singapore tertiary cancer center. The European Organization for Research and Treatment-QOL questionnaire and breast cancer specific module (EORTC QLQ-C30 and QLQ-BR23) were used to measure the HRQOL among women with breast cancer. All statistical tests were performed using SPSS Version 18. The reliability of the EORTC QLQ-C30 and QLQ-BR23 questionnaires was examined using Cronbach's alpha test. EORTC QLQ-C30 was validated against EuroQol Group's 5-domain questionnaires (EQ5D) by examining its concurrent validity using Pearson Product Moment Correlation to calculate the total scores.Results:The Cronbach's alpha coefficient results for EORTC QLQ-C30 and QLQ BR-23 were 0.846 and 0.873 respectively which suggested relatively good internal consistency. The correlation between EORTC QLQ-C30 and EQ5D QOL instruments demonstrated a modest linear relationship (r=0.597; P<0.001) that indicated a moderately strong correlation between the two measures. The study showed that Singaporean women with breast cancer had enjoyed high levels of HRQOL during their first 4 years of survivorship but they had significant concern over the financial impact of breast cancer. One of the key findings was younger women had experienced more physical and psychosocial concerns than older women.Conclusion:The EORTC QLQ-C30 and QLQ-BR23 questionnaires are feasible and promising instruments to measure the levels of HRQOL in Singaporean women with breast cancer in future studies.

Measurement Properties of the Eight-Item Abbreviated Functional Assessment of Cancer Therapy—Breast Symptom Index and Comparison With Its 37-Item Parent Measure

ContextThe Functional Assessment of Cancer Therapy—Breast Symptom Index (FBSI) is an eight-item instrument extracted from the Functional Assessment of Cancer Therapy—Breast (FACT-B). There has been no formal assessment of this eight-item version. ObjectivesThis study aimed to examine the measurement properties of and comparability between the English and the Chinese versions of the FBSI and to compare it with its parent instrument, the FACT-B, in breast cancer patients in Singapore. MethodsThis was an observational study of 271 breast cancer patients. Known-group validity of FBSI scores was assessed using four health indicators. Convergent and divergent validity was examined by correlation coefficients between the FBSI and the FACT-B. Responsiveness was assessed in relation to longitudinal changes in performance status. Test-retest reliability was evaluated by the intraclass correlation coefficient. Multiple regression analyses were performed to compare the scores on the two language versions. Receiver operating characteristic curve analyses were used for comparison between the FBSI and the FACT-B. ResultsFor both language versions, the FBSI demonstrated known-group validity, convergent and divergent validity, and sufficient test-retest reliability (intraclass correlation coefficient=0.75–0.77). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. No practical significant difference was found in the outcomes between the two language versions despite minor difference in one item. The FBSI performed comparably with the FACT-B. ConclusionThe English and Chinese versions of the FBSI are valid and reliable and provide comparable FBSI scores. The English version is responsive to change, whereas the responsiveness of the Chinese version warrants further study.

The English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) were valid and reliable and provided comparable scores in Asian breast cancer patients

To examine the measurement properties of and comparability between the English and Chinese versions of the five-level EuroQoL Group's five-dimension questionnaire (EQ-5D) in breast cancer patients in Singapore. This is an observational study of 269 patients. Known-group validity and responsiveness of the EQ-5D utility index and visual analog scale (VAS) were assessed in relation to various clinical characteristics and longitudinal change in performance status, respectively. Convergent and divergent validity was examined by correlation coefficients between the EQ-5D and a breast cancer-specific instrument. Test-retest reliability was evaluated. The two language versions were compared by multiple regression analyses. For both English and Chinese versions, the EQ-5D utility index and VAS demonstrated known-group validity and convergent and divergent validity, and presented sufficient test-retest reliability (intraclass correlation = 0.72 to 0.83). The English version was responsive to changes in performance status. The Chinese version was responsive to decline in performance status, but there was no conclusive evidence about its responsiveness to improvement in performance status. In the comparison analyses of the utility index and VAS between the two language versions, borderline results were obtained, and equivalence cannot be definitely confirmed. The five-level EQ-5D is valid, responsive, and reliable in assessing health outcome of breast cancer patients. The English and Chinese versions provide comparable measurement results.

Measurement properties of the English and Chinese versions of the Functional Assessment of Cancer Therapy—Breast (FACT-B) in Asian breast cancer patients

The objective of the study was to examine the measurement properties of and comparability between the English and Chinese versions of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in breast cancer patients in Singapore. This is an observational study of 271 Singaporean breast cancer patients. The known-group validity of FACT-B total score and Trial Outcome Index (TOI) were assessed in relation to performance status, evidence of disease, and treatment status cross-sectionally; responsiveness to change was assessed in relation to change in performance status longitudinally. Internal consistency and test-retest reliability were evaluated by the Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. Multiple regression analyses were performed to compare the scores on the two language versions, adjusting for covariates. The FACT-B total score and TOI demonstrated known-group validity in differentiating patients with different clinical status. They showed high internal consistency and test-retest reliability, with Cronbach's alpha ranging from 0.87 to 0.91 and ICC ranging from 0.82 to 0.89. The English version was responsive to the change in performance status. The Chinese version was shown to be responsive to decline in performance status but the sample size of Chinese-speaking patients who improved in performance status was too small (N = 6) for conclusive analysis about responsiveness to improvement. Two items concerning sexuality had a high item non-response rate (50.2 and 14.4%). No practically significant difference was found in the total score and TOI between the two language versions despite minor differences in two of the 37 items. The English and Chinese versions of the FACT-B are valid, responsive, and reliable instruments in assessing health-related quality of life in breast cancer patients in Singapore. Data collected from the English and Chinese versions can be pooled and either version could be used for bilingual patients.

Impact of Older Age on Presentation and Management of Breast Cancer in the Multi-Ethnic Population of Singapore.

Abstract Background: Studies in Caucasian populations have shown that older breast cancer patients are less likely to be treated according to standard guidelines and that this under-treatment is strongly associated with impaired survival. In Asia, where population sizes and life expectancy rates are rising, the number of older women developing breast cancer is growing rapidly. This study aims to evaluate characteristics and treatment patterns of older breast cancer patients in the multi-ethnic population of Singapore, where breast cancer rates have tripled over the past three decades.Methods: This study includes all 2547 women, diagnosed with breast cancer between 1995 and 2006 at the National University Hospital in Singapore. Patients were classified into younger (&amp;lt; 65 years, n=2220) and older (&amp;gt;= 65 years, n=327). Differences in patient and tumor characteristics and treatment between older and younger age groups were explored using multivariate logistic regression models.Results: Even though older Singapore breast cancer patients had more favorable tumor characteristics than younger ones (better tumor differentiation, more often expressing estrogen and progesterone receptors), they presented significantly more often with stage III (adjusted Odds Ratio [ORadj] 1.57, 95%CI 1.0-2.4) and metastatic disease (ORadj 4.3, 95%CI 2.9-6.5). Elderly women were at increased risk not to receive breast surgery (ORadj 1.61, 95%CI 1.0-2.6) and axillary clearance (ORadj 1.74, 95%CI 1.2-2.6). In case of stage I disease, older women were significantly less likely than younger women to be treated with breast conserving surgery (ORadj 0.31, 95%CI 0.2-0.5).Conclusion: Similar to their Caucasian counterparts, older Asian breast cancer patients in Singapore are diagnosed at a later stage and receive less often standard treatment than younger women. Further studies are being undertaken to estimate the impact of these discrepancies on outcome. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3078.

The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives.

The purpose of this study was to determine the prevalence of BRCA1 mutations in Chinese breast cancer patients in Singapore. BRCA1 analysis was conducted in consecutive patients with breast cancer before the age of 40 years (76 women), or whose relatives had breast or ovarian cancer (16 women). Ten patients had both early onset breast cancer and affected relatives. Genomic DNA from peripheral mononuclear blood cells was studied by using the protein transcription–translation assay (exon 11) and single-strand conformational polymorphism, with subsequent DNA sequencing. All six disease-causing mutations occurred in women under 40 years (8.6%) with three occurring in patients under 35 years (three out of 22 patients, 13.6%). Mis-sense mutations of unknown significance were found in three patients. Two of the ten women with affected relatives under 40 years had BRCA1 mutations. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that observed in Caucasian women. Most Chinese patients with affected relatives were not carriers of BRCA1 mutations. © 2000 Cancer Research Campaign