Presentation of Breast Cancer and Impact of Patient Navigation on Timeliness of Diagnosis and Treatment and on Adherence to Treatment Recommendations in a Multicenter Network in Malaysia.

PURPOSE: Breast cancer deaths disproportionately affect women living in low- and middle-income countries (LMICs). Patient navigation has emerged as a cost-effective and impactful approach to enable women with symptoms or suspicious mammogram findings to access timely diagnosis and patients with breast cancer to access timely and appropriate multimodality treatment. However, few studies have systematically evaluated the impact of patient navigation on timeliness of diagnosis and treatment in LMICs. METHODS: We established a nurse- and community-navigator-led navigation program in breast clinics of four public hospitals located in Peninsular and East Malaysia and evaluated the impact of navigation on timeliness of diagnosis and treatment. RESULTS: Patients with breast cancer treated at public hospitals reported facing barriers to accessing care, including having a poor recognition of breast cancer symptoms and low awareness of screening methods, and facing financial and logistics challenges. Compared with patients diagnosed in the previous year, patients receiving navigation experienced timely ultrasound (84.0% v 65.0%; P < .001), biopsy (84.0% v 78.0%; P = .012), communication of news (63.0% v 40.0%; P < .001), surgery (46% v 36%; P = .008), and neoadjuvant therapy (59% v 42%, P = .030). Treatment adherence improved significantly (98.0% v 87.0%, P < .001), and this was consistent across the network of four breast clinics. CONCLUSION: Patient navigation improves access to timely diagnosis and treatment for women presenting at secondary and tertiary hospitals in Malaysia.

Perceptions, attitudes and beliefs towards soya among healthy Asian women participating in a soya randomised controlled trial.

The soya-breast cancer risk relationship remains controversial in Asia due to limited and inconsistent research findings and is exacerbated by difficulties in recruiting and retaining participants in intervention trials. Understanding public perceptions towards soya is important for designing effective intervention trials. Here, we administered a close-ended, quantitative survey to healthy, peri- and post-menopausal Asian women in the Malaysian Soy and Mammographic Density (MiSo) Study to assess perception towards soya and explore motivators and barriers that affect study adherence using the Capability, Opportunity, Motivation and Belief (COM-B) Model and Theoretical Domains Framework (TDF). Of 118 participants, the majority reported the belief that soya promotes good health (Supplement = 85⋅7 %, Diet = 90⋅0 %, Control = 87⋅9 %). Most participants reported obtaining information about soya from the internet (Supplement = 61⋅0 %, Diet = 55⋅3 %, Control = 35⋅9 %), while health professionals were least reported (Supplement = 9⋅8 %, Diet = 7⋅9 %, Control = 5⋅1 %). Stratified analyses by study completion and adherence status yielded comparable findings. By the end of the study, dietary arm participants reported a strong belief that soya has no impact on their health (Supplement = 7⋅1 % v. Diet = 20⋅0 % v. Control = 0⋅0 %, P = 0⋅012). Motivation and opportunity strongly facilitated soya consumption, while psychological capability was the most common barrier to consumption though less evident among dietary arm participants. While most Asian women have a positive perception towards soya, theory-based intervention trials are warranted to understand the perception-study adherence relationship and to accurately inform the public of the health effects of soya.

Barriers to help-seeking for Malaysian women with symptoms of breast cancer: a mixed-methods, two-step cluster analysis.

BACKGROUND: Improving help-seeking behaviour is a key component of down-staging breast cancer and improving survival, but the specific challenges faced by low-income women in an Asian setting remain poorly characterized. Here, we determined the extent of help-seeking delay among Malaysian breast cancer patients who presented at late stages and explored sub-groups of women who may face specific barriers. METHODS: Time to help-seeking was assessed in 303 women diagnosed with advanced breast cancer between January 2015 and March 2020 at a suburban tertiary hospital in Malaysia. Two-step cluster analysis was conducted to identify subgroups of women who share similar characteristics and barriers. Barriers to help-seeking were identified from nurse interviews and were analyzed using behavioural frameworks. RESULTS: The average time to help-seeking was 65 days (IQR = 250 days), and up to 44.5% of women delayed by at least 3 months. Three equal-sized clusters emerged with good separation by time to help-seeking (p < 0.001). The most reported barrier across clusters was poor knowledge about breast health or breast cancer symptoms (36.3%), regardless of help-seeking behaviour (p = 0.931). Unexpectedly, women with no delay (9 days average) and great delay (259 days average) were more similar to each other than to women with mild delays (58 days average), but, women who experienced great delay reported poor motivation due to fear and embarrassment (p = 0.066) and a lack of social support (p = 0.374) to seek help. CONCLUSIONS: Down-staging of breast cancer in Malaysia will require a multi-pronged approach aimed at modifying culturally specific social and emotional barriers, eliminating misinformation, and instilling motivation to seek help for breast health for the women most vulnerable to help-seeking delays.

A Randomized Controlled Trial of Soy Isoflavone Intake on Mammographic Density among Malaysian Women.

Soy intake is associated with lower breast cancer risk in observational studies concerning Asian women, however, no randomized controlled trials (RCT) have been conducted among Asian women living in Asia. This three-armed RCT assessed the effects of one-year soy isoflavone (ISF) intervention on mammographic density (MD) change among healthy peri- and postmenopausal Malaysian women. This study was registered at ClinicalTrials.gov (NCT03686098). Participants were randomized into the 100 mg/day ISF Supplement, 50 mg/day ISF Diet, or control arm, and assessed for change in absolute and relative dense area from digital mammograms conducted at enrolment and after 12 months, compared over time across study arms using Kruskal-Wallis tests. Out of 118 women enrolled, 91 women completed the intervention, while 27 women (23%) were lost in follow up. The ISF supplement arm participants observed a larger decline in dense area (−1.3 cm2), compared to the ISF diet (−0.5 cm2) and control arm (−0.8 cm2), though it was not statistically significant (p = 0.48). Notably, among women enrolled within 5 years of menopause; dense area declined by 6 cm2 in the ISF supplement arm, compared to <1.0 cm2 in the control arm (p = 0.13). This RCT demonstrates a possible causal association between soy ISF intake and MD, a biomarker of breast cancer risk, among Asian women around the time of menopause, but these findings require confirmation in a larger trial.

Risk stratification and assessment framework for international travel and border measures amidst the COVID-19 pandemic - A Malaysian perspective.

BACKGROUND: Guided by the best practices adapted from national and international bodies including the World Health Organization (WHO), the Centers for Disease Control (CDC), and the UK Joint Biosecurity Centre (JBC), this paper aims to develop and provide an empirical risk stratification and assessment framework for advancing the safe resumption of global travel during the COVID-19 pandemic. METHOD: Variables included in our model are categorized into four pillars: (i) incidence of cases, (ii) reliability of case data, (iii) vaccination, and (iv) variant surveillance. These measures are combined based on weights that reflect their corresponding importance in risk assessment within the context of the pandemic to calculate the risk score for each country. As a validation step, the outcome of the risk stratification from our model is compared against four countries. RESULTS: Our model is found to have good agreement with these benchmarked risk designations for 27 out of the top 30 countries with the strongest travel ties to Malaysia (90%). Each factor within this model signifies its importance and can be adapted by governing bodies to address the changing needs of border control policies for the recommencement of international travel. CONCLUSION: In practice, the proposed model provides a turnkey solution for nations to manage transmission risk by enabling stakeholders to make informed, evidence-based decisions to minimize fluctuations of imported cases and serves as a structure to support the improvement, planning, and activation of public health control measures.

Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high-income countries.

OBJECTIVES: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women. METHODS: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients. RESULTS: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes. CONCLUSION: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes.

Measurement challenge: protocol for international case-control comparison of mammographic measures that predict breast cancer risk.

INTRODUCTION: For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk. METHODS AND ANALYSIS: The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk. ETHICS AND DISSEMINATION: Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).

Feasibility of Patient Navigation to Improve Breast Cancer Care in Malaysia.

PURPOSE: Late stage at presentation and poor adherence to treatment remain major contributors to poor survival in low- and middle-income countries (LMICs). Patient navigation (PN) programs in the United States have led to improvement in diagnostic or treatment timeliness, particularly for women in lower socioeconomic classes or minority groups. To date, studies of PN in Asia have been limited. We aimed to assess the feasibility of PN in a state-run hospital in an LMIC and to report the impact on diagnostic and treatment timeliness for patients in its first year of implementation. METHODS: We established PN in a dedicated breast clinic of a Malaysian state-run hospital. We compared diagnostic and treatment timeliness between navigated patients (n = 135) and patients diagnosed in the prior year (n = 148), and described factors associated with timeliness. RESULTS: Women with PN received timely mammography compared with patients in the prior year (96.4% v 74.4%; P < .001), biopsy (92.5% v 76.1%; P = .003), and communication of news (80.0% v 58.5%; P < .001). PN reduced treatment default rates (4.4% v 11.5%; P = .048). Among navigated patients, late stage at presentation was independently associated with having emotional and language barriers ( P = .01). Finally, the main reason reported for delay, default, or refusal of treatment was the preference for alternative therapy. CONCLUSION: PN is feasible for addressing barriers to cancer care when integrated with a state-run breast clinic of an LMIC. Its implementation resulted in improved diagnostic timeliness and reduced treatment default. Wider adoption of PN could be a key element of cancer control in LMICs.

A case-control study of breast cancer risk factors in 7,663 women in Malaysia.

BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women. METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity. RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy. CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

Physical activity and mammographic density in an Asian multi-ethnic cohort.

BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density. METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders. RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density. CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

Performance of a subsidised mammographic screening programme in Malaysia, a middle-income Asian country.

BACKGROUND: The incidence of breast cancer in Asia is increasing because of urbanization and lifestyle changes. In the developing countries in Asia, women present at late stages, and mortality is high. Mammographic screening is the only evidence-based screening modality that reduces breast cancer mortality. To date, only opportunistic screening is offered in the majority of Asian countries because of the lack of justification and funding. Nevertheless, there have been few reports on the effectiveness of such programmes. In this study, we describe the cancer detection rate and challenges experienced in an opportunistic mammographic screening programme in Malaysia. METHODS: From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined. RESULTS: The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities. DISCUSSION: The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms. CONCLUSION: Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.

Differences in mammographic density between Asian and Caucasian populations: a comparative analysis.

PURPOSE: Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors. METHODS: Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts. RESULTS: Compared to Caucasian women, percent density was 2.0% higher among Asian women (p < 0.001), and dense volume was 5.7 cm3 higher among pre-menopausal Asian women (p < 0.001). Dense volume was 3.0 cm3 lower among post-menopausal Asian women (p = 0.009) compared to post-menopausal Caucasian women, and this difference was attributed to population differences in height, weight, and parity (p < 0.001). CONCLUSIONS: Our analysis suggests that among post-menopausal women, population differences in mammographic density and risk to breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.

International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries.

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses.