Divergent breast cancer incidence trends by hormone receptor status in the state of Sarawak, Malaysia.

Recent studies from high-risk countries such as the US, Denmark and Ireland have shown rising incidence rates of hormone receptor (HR)-positive and falling rates of HR-negative breast cancers (BC). However, it remains unclear whether a similar pattern occurs in low-risk countries. Detailed clinical and risk factor data were collected from 2,977 female invasive BC patients (≥20 years) in Sarawak General Hospital, Malaysia, representing 93% of the population. The population-at-risk was obtained from the Department of Statistics Malaysia. Secular trends in age-standardized incidence rates were assessed using estimated average annual percent changes. Associations between established BC risk factors and tumor subtypes defined by HR or joint human epidermal growth factor receptor 2 (HR/HER2) status were examined by case-case comparisons using logistic regression. From 2006 to 2015, incidence rates increased for HR-positive cancers by 4.46%/year (95% CI = 2.19-6.78) and decreased for HR-negative cancers by 2.29%/year (95% CI = -4.31 to -0.24). When further stratified by HER2, the most contrasting difference in linear trends was observed between HR+/HER2- and HR-/HER2- subtypes. After controlling for potential confounders, cases with excess body weight (ORoverweight vs. normal = 0.82; 95% CI = 0.69-0.98; ORobese vs. normal = 0.62; 95% CI = 0.48-0.80), later age at first birth (OR≥26 years vs. <23 years = 0.82; 95% CI = 0.66-1.02), nulliparity (ORnulliparous vs. <23 years = 0.74; 95% CI = 0.59-0.94) and never-breastfeeding (ORnever vs. ever = 0.73; 95% CI = 0.55-0.97) were less frequent among HR-negative cases than among HR-positive cases. Diverging incidence trends by HR expression were similar in Sarawak and Western countries, possibly reflecting changes in the prevalence of risk factors with opposing effects by tumor subtypes in low- and high-risk populations.

Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia.

PURPOSE: To characterize the spectrum of germline mutations in BRCA1, BRCA2, and PALB2 in population-based unselected breast cancer cases in an Asian population. METHODS: Germline DNA from 467 breast cancer patients in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated, was sequenced for the entire coding region of BRCA1; BRCA2; PALB2; Exons 6, 7, and 8 of TP53; and Exons 7 and 8 of PTEN. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants, and variants that disrupt splice site. RESULTS: We found 27 pathogenic variants (11 BRCA1, 10 BRCA2, 4 PALB2, and 2 TP53) in 34 patients, which gave a prevalence of germline mutations of 2.8, 3.23, and 0.86% for BRCA1, BRCA2, and PALB2, respectively. Compared to mutation non-carriers, BRCA1 mutation carriers were more likely to have an earlier age at onset, triple-negative subtype, and lower body mass index, whereas BRCA2 mutation carriers were more likely to have a positive family history. Mutation carrier cases had worse survival compared to non-carriers; however, the association was mostly driven by stage and tumor subtype. We also identified 19 variants of unknown significance, and some of them were predicted to alter splicing or transcription factor binding sites. CONCLUSION: Our data provide insight into the genetics of breast cancer in this understudied group and suggest the need for modifying genetic testing guidelines for this population with a much younger age at diagnosis and more limited resources compared with Caucasian populations.

Breast cancer research in Asia: adopt or adapt Western knowledge?

The incidence and mortality of breast cancer continues to rise rapidly in Asian countries. However, most of our current knowledge on breast cancer has been generated in Western populations. As the socio-economic profile, life style and culture of Asian and Western women are substantially different, and genetic backgrounds vary to some extent, we need to answer the question on whether to 'adopt' or 'adapt' Western knowledge before applying it in the Asian setting. It is generally accepted that breast cancer risk factors, which have mainly been studied in Western populations are similar worldwide. However, the presence of gene-environment or gene-gene interactions may alter their importance as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, are increasingly shown to be 'setting specific' and must therefore be validated in Asian women before implementing them in clinical care in Asia. Interventional research findings from Caucasian patients may not be applicable in patients in Asia due to differences in tumour biology/profiles, metabolism of drugs and also health beliefs which can influence treatment acceptance and adherence. While breast cancer research in Asia is warranted in all domains of medical research, it is felt that for Asian breast cancer patients, needs are highest for diagnostic and prognostic studies. International clinical trials meanwhile need to include breast cancer patients from various Asian settings to provide an insight into the effectiveness of new treatment modalities in this part of the world.

Cervical cancer screening: patients understanding in major hospitals in Malaysia.

We studied women with cervical cancer to determine whether they had had a Pap smear within the 3 years preceding cancer development and their understanding of screening for this cancer. The study had 2 parts; Pathology Data and Survey Data. For pathology data, all cases of cervical cancer diagnosed in 2000-2006 were retrieved from eight hospitals and Pap smear history was obtained from clinical records. For the Survey data; patients who were still undergoing treatment in some of these hospitals and three others were administered structured questionnaires to determine their awareness about screening. The results showed 1431 cases of cervical cancer in women aged 25-85 were diagnosed in these hospitals. Most had not had a Pap smear within 3 years before cancer development. The percentages of patients who had had Pap smear ranged from 0-12%. Questionnaires were returned by 221 patients; 56.3% had none or only primary education and 61.1% had a household income of RM 1,000 or less. Level of education and the household income were strongly associated (p<0.05) with knowledge and having had a Pap test. The main reasons cited for not having had a Pap smear were "Never heard about it" (36.2%), "Shy" (10.4%), "Afraid to do it" (13.1%), "Think the test is not important" (8.1%) and "No encouragement from family" (4.5%). A large majority (95.9%) of the patients did not know the optimal interval. In conclusion, a large number of cervical cancer patients had not had a Pap smear within 3 years preceding cancer development and most had inadequate knowledge about this screening test.

Preliminary results from the pilot study on the National Cancer Patient Registry--Cervical Cancer.

Carcinoma of the cervix is the most common malignancy in many developing countries. The purpose of this pilot study on cervical cancer patients treated at selected sites in Malaysia is to examine the achievability of collecting information on patients. The data was collected from the medical records of the patients using case report form. The results reveal that more than 90% of the forms had completed data from all sites. The pilot study has demonstrated that it is feasible to register and collect information on cervical cancer patients using the case report forms. Treatment outcome obtained from this data will form the baseline to establish existing clinical practice and will be useful for treating physicians to monitor the treatment outcome and the late complications and with longer followup to measure the disease free and overall survival. In addition, it is an useful tool as the national indicator.

What doctors know about cancer pain management: an exploratory study in Sarawak, Malaysia.

Effective cancer pain management is influenced by the attitudes and knowledge of treating physicians. A survey was conducted among the total population of government hospital doctors of Sarawak to study the barriers to cancer pain management. Two hundred and fifty-three respondents (83%) completed the survey. The study results highlight that knowledge about cancer pain management was low and barriers to morphine prescription were high. A majority of doctors were deterred from using morphine because of fear of addiction (36.5%) and respiratory depression (53.1%). Only 16.2% of the doctors chose the oral mode of administration to treat pain, furthermore 25% prescribed morphine on "PRN" basis. Doctors with undergraduate study in oncology consistently answered better suggesting that the situation can be improved by education. This study showed that barriers to morphine prescription and knowledge deficit amongst government doctors in Sarawak are strong but similar to those reported in western countries few years ago.

High incidence of nasopharyngeal carcinoma in native people of Sarawak, Borneo Island.

Nasopharyngeal cancer (NPC) is generally a rare malignancy with a few well-known exceptions, notably South-East China. In this article, we describe evidence of a high risk of NPC in the population of Sarawak State, Malaysia, and particularly in one native ethnic group. Sarawak State is one of the two provinces of Malaysia located on the island of Borneo. The native population (71.6%) includes the Iban, Malay, Bidayuh, Melanau, and diverse smaller ethnic groups. The Chinese are the largest nonindigenous group (27.5%). We identified 392 newly diagnosed cases (292 males and 100 females) of NPC in 1996-1998 in Malaysian citizens, permanent residents of Sarawak. Age-standardized rates by sex and ethnic group were compared with the highest rates in the world. The age-adjusted rate (ASR) in Sarawak residents was 13.5/100,000 [95% confidence interval (CI) 12.2-15.0] and 6.2/100,000 (95% CI 5.7-6.7) in males and females, respectively. The risk in the Bidayuh people was 2.3-fold (M) and 1.9-fold (F) higher than the Sarawak average, and about 50% higher than that in Hong Kong-the highest recorded by any population-based registry for the same period. Local dietary habits, environmental exposures, and genetic susceptibility deserve investigation in this population.