Breast cancer is one of the leading cancers world-wide. While the incidence in developing countries is lower than in developed countries, the mortality is much higher. Of the estimated 1 600 000 new cases of breast cancer globally in 2012, 794 000 were in the more developed world compared to 883 000 in the less developed world; however, there were 198 000 deaths in the more developed world compared to 324 000 in the less developed world (data from Globocan 2012, IARC). Survival from breast cancer depends on two main factors--early detection and optimal treatment. In developing countries, women present with late stages of disease. The barriers to early detection are physical, such as geographical isolation, financial as well as psychosocial, including lack of education, belief in traditional medicine and lack of autonomous decision-making in the male-dominated societies that prevail in the developing world. There are virtually no population-based breast cancer screening programs in developing countries. However, before any screening program can be implemented, there must be facilities to treat the cancers that are detected. Inadequate access to optimal treatment of breast cancer remains a problem. Lack of specialist manpower, facilities and anticancer drugs contribute to the suboptimal care that a woman with breast cancer in a low-income country receives. International groups such as the Breast Health Global Initiative were set up to develop economically feasible, clinical practice guidelines for breast cancer management to improve breast health outcomes in countries with limited resources.
The incidence of breast cancer is rising in low- and middle-income countries (LMICs) due to 'westernization' of risk factors for developing breast cancer. However, survival remains low because of barriers in early detection and optimal access to treatment, which are the two main determinants of breast cancer outcome. A multidisciplinary approach to treatment gives the best results. An accurate diagnosis is dependent on a reliable pathology service, which will provide an adequate pathology report with prognostic and predictor information to allow optimal oncological treatment. Stratification of clinical practice guidelines based on resource level will ensure that women will have access to treatment even in a low-resource setting. Advocacy and civil society play a role in galvanizing the political will required to meet the challenge of providing opportunities for breast cancer control in LMICs. Collaboration between high-income countries and LMICs could be a strategy in facing these challenges.
Direct tumour extension into the internal jugular veins (IJV) and right atrium in thyroid cancer is extremely uncommon. We report three cases of advanced thyroid cancer invading into the IJV and right atrium. All three patients had well-differentiated thyroid cancer and presented with typical clinical picture of the superior cava syndrome coupled with significant compressive symptoms. Two patients had obvious tumour thrombus extending to the superior vena cava (SVC) and right atrium, whilst in one patient, the thrombus extended to the SVC close to the edge of the right atrium. In all three patients, the intraluminal tumour thrombus was clinically palpable. Involvement of the IJV, SVC and right atrium was confirmed with computed tomography (CT) scan and echocardiography. The decision to extract the thrombus transcervically was made on the basis of the positive "ring sign", which is a thin rim of contrast surrounding the tumour thrombus documented on CT. All three patients underwent total thyroidectomy with segmental resection and ligation of the IJV. The tumour thrombus was successfully extracted transcervically. The histopathology report confirmed follicular carcinoma in all three patients. Two patients had radioiodine ablation therapy postoperatively, and were well 18 months after operation. One patient who had lung metastases documented on chest CT succumbed to the disease due to massive haemoptysis 3 weeks after operation.
Advanced breast cancer presentation remains a large obstacle in lowering mortality rates in low- and middle-resource countries. This study aims to explore the reasons why women present with breast cancer at an advanced stage.
The aim of this study was to assess why women delay in getting treatment (i.e. surgery) for breast cancer, as well as to explore on what type of issues are involved in such delay cases. Basic interpretative of qualitative methodology was applied to construct the reality of delay phenomena, and its interaction with social worlds. Six themes were identified: new conception of breast cancer treatment, psychological defenses, health support system, symtomatology experience, model and barriers. The delay issue in breast cancer requires attention as a multidimensional problem as this will facilitate more comprehensive and effective intervention to reduce delay.
INTRODUCTION: Advanced presentation of breast cancer and the problem of late diagnosis is well documented. Patient delay beyond three months has been shown to reduce survival. This paper aims to explore the experience of Malaysian women presenting with advanced breast cancer with regards to their interpretation of breast symptoms.
METHOD: Purposive sampling of 19 breast cancer patients presenting with delayed treatment and/ or advanced cancer diagnosed within two years at the University Malaya Medical Centre, Kuala Lumpur were carried out. In-depth interviews were conducted using a self-devised interview guide. The interview guide covered the journey of the patient from discovering of symptoms to their present state. The audiotaped interviews were transcribed verbatim. NVivo 8 qualitative software was utilised for data management. Grounded theory with thematic analysis was utilised.
RESULTS: Nine women delayed seeking diagnosis although recognizing the symptom, five did not recognize symptom, three delayed treatment and two did not delay health attention. Themes that emerged with regards to triggering help seeking behavior were: a) poor symptom knowledge and recognition; b) importance of knowledge of the disease and its' outcomes; c) role of coping mechanisms and affect; and lastly d) role of significant others in appraising a breast symptom.
CONCLUSION: Symptom recognition remains an important public health issue in Malaysia. Educating women, their significant others and primary health and primary care providers in detecting early staged breast cancer are needed. Supporting and sanctioning women with breast symptoms are important. The psycho-social-cultural model of symptom appraisal may serve as an important addition to the fight against cancer in countries that do not have the resources for population based screening mammogram programmes.
The purpose of the present study was to evaluate the association between TCF7L2 rs12255372(G/T) or rs7903146(C/T) polymorphism and breast cancer risk, and clinico-pathologic characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. The allele (P = 0.033) frequency of rs7903146 (T) polymorphism was significantly higher in the cancer patients than normal individuals. No significant association was demonstrated between CT (OR(adj) = 1.386; 95% CI, 0.985-1.949) or TT (OR(adj) = 1.579; 95% CI, 0.869-2.870) genotype and breast cancer risk. However, women who were carriers of T allele (OR(adj) = 1.316; 95% CI, 1.022-1.695) or T allele genotype (OR(adj) = 1.419; 95% CI, 1.027-1.960) showed significant increased risk of breast cancer. Women who were GT heterozygotes (OR(adj) = 1.329; 95% CI, 0.948-1.862) or TT homozygotes (OR(adj) = 1.574; 95% CI, 0.829-2.987), and carriers of T allele genotype (OR(adj) = 1.365; 95% CI, 0.989-1.883) or T allele (OR(adj) = 1.284; 95% CI, 0.995-1.657) were not associated with breast cancer risk. The rs7903146(T) allele genotype was significantly associated with nodal involvement (P = 0.003) but rs12255372 (T) allele genotype was not associated with the clinico-pathologic characteristics. In conclusion, our findings suggest that rs7903146 (T) variant may elevate the risk of breast cancer, thus could be a potential candidate for breast cancer susceptibility. The variant may also increase the metastatic potential of the tumor.
The genotype analysis of the Gly and Arg allele at codon 388 of fibroblast growth factor receptor-4 (FGFR4) gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The aim of the present study was to evaluate the association between the FGFR4 Gly388Arg polymorphism and breast cancer risk as well as clinicopathological parameters of the patients. The Gly/Gly, Gly/Arg, Arg/Arg, and Arg allele genotypes were detected in 46.3%, 44.4%, 9.3%, and 53.7% of breast cancer cases, respectively. The distribution of genotype (p = 0.204) and allele (p = 0.086) frequencies of FGFR4 polymorphism were not significantly different between the breast cancer cases and normal individuals. Women who were Arg/ Arg homozygotes (OR = 1.714, 95% CI 0.896-3.278), Gly/Arg heterozygotes (OR = 1.205, 95% CI 0.863-1.683), carriers of Arg allele genotype (OR = 1.269, 95% CI 0.921-1.750), or Arg allele (OR = 1.246, 95% CI 0.970-1.602) were not associated with breast cancer risk. The Arg allele genotype was significantly associated with lymph node metastases (p = 0.001) but not with other clinicopathological parameters. Our findings suggest that the polymorphic variant at codon 388 of FGFR4 gene does not confer increased risk to breast cancer development but it may be a potential genetic marker for tumor prognosis.
The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.
Study site: Universiti Malaya Medical Centre (UMMC)
The purpose of this study was to investigate the association between the peptidyl-propyl-cis/trans isomerase 1 (PIN1) -842(G > C) and -667(T > C) polymorphic variants and breast cancer risk among Malaysian ethnic groups namely the Malays, Chinese and Indians, as well as clinico-pathological characteristics of the patients.
Intussusception due to small intestinal polyps in Peutz-Jeghers syndrome represents a significant clinical challenge. Neither pure surgical nor endoscopic approaches alone are effective in the long-term management of this problem. We describe a combined approach using both surgery and small bowel endoscopy in the management of this condition, which resulted in both immediate and long-term success. Although not new, we believe this approach remains relevant despite recent technological advancements in this area.
The C1772T, G1790A and C111A polymorphisms of Hypoxia-inducible factor-1alpha (HIF-1alpha) gene were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Genomic DNA was extracted from the blood samples collected from 410 breast cancer patients and 275 normal and healthy women. We investigated the association between HIF-1alpha polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of C1772T (P=0.0093 vs P=0.0024) polymorphism were significantly different between the breast cancer cases and normal subjects but similar association was not observed for G1790A (P>0.05) and C111A (P>0.05) polymorphisms, respectively. Women who were CT heterozygotes (OR=1.51; 95% CI, 1.01-2.25), TT homozygotes (OR=4.03; 95% CI, 1.09-17.60) and carriers of T allele genotype (OR=1.65; 95% CI, 1.13-2.43) were significantly associated with increased risk of breast cancer. Significant relationship was observed also between T allele and breast cancer risk (OR=1.69; 95% CI, 1.20-2.40). Clinico-pathological analysis showed that 1772T allele genotype was significantly associated with nodal metastases (P=0.0478) but independent of ER status, tumor grade and patients' age (P>0.05). Our observations suggest that the polymorphic allele of C1772T may be associated with increased risk of developing breast cancer, and presence of 1772T allele may be a useful genetic marker for tumor prognosis.
Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.
Data from the National Cancer Registry of Malaysia for 2004 provide an age-standardised incidence rate (ASR) of 46.2 per 100,000 women. This means that approximately 1 in 20 women in the country develop breast cancer in their lifetime. However, the rate differs between the three main races, the Malays, Chinese and Indians. The age standardized incidence in Chinese is the highest, with 59.7 per 100,000, followed by the Indians at 55.8 per 100,000. The Malays have the lowest incidence of 33.9 per 100,000. This translates into 1 in 16 Chinese, 1 in 16 Indian and 1 in 28 Malay women developing breast cancer at some stage in their lives. The commonest age at presentation is between 40-49 years, with just over 50% of the cases under the age of 50 years, 16.8% below 40, and 2% under 30. Some 55.7% of all cases were found to be ER positive. The commonest presenting symptom was a lump in the breast in over 90% of cases, generally felt by the woman herself. The mean size of the lump was 4.2 cm, and on average, the women waited 3 months before seeking medical attention. Over the 12-year period from 1993 to 2004, about 60-70% of women presented with early stage (Stages 1-2) while 30-40% presented with late breast cancer (Stages 3-4). Especially Malays present at later stages and with larger tumours. Consequently their survival is worse than with Chinese and Indian women. The challenge in Malaysia is to be able to provide a comprehensive service in the diagnosis and treatment of breast cancer, and this requires training of a team of health professionals dedicated to breast health, such as breast surgeons, radiologists specializing in breast imaging, breast pathologists, plastic surgeons specializing in breast reconstruction, medical and radiation oncologists, psycho-oncologists, counselors, and breast nurses. Advocacy can play a role here in galvanizing the political will to meet this challenge.
The p27 V109G polymorphism was investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 230 breast cancer patients and 200 normal and healthy women who had no history of breast disease or breast cancer. We evaluated the association between the p27 polymorphism and breast cancer risk, and clinico-pathological parameters in the population. The distribution of genotype and allele frequencies of p27 V109G polymorphism were not significantly different between the breast cancer cases and normal subjects (P=0.376). Women who were homozygous (OR=1.73; 95% CI, 0.62-4.92) or heterozygous (OR=1.26; 95% CI, 0.75-2.12) for G allele, or carriers of G allele genotype (OR=1.34; 95%, 0.83-2.16) or G allele (OR=1.36; 95% CI, 0.90-2.05) were not associated with breast cancer risk. No significant correlation was noted between G allele genotype and breast cancer risk among patients under 50 (OR=1.28; 95% CI, 0.62-2.66) or 50 years and older (OR=1.38; 95% CI, 0.71-2.66) at diagnosis. The G allele genotype was significantly associated with lymph node metastases but independent of ER status and histological grade. In conclusion, the polymorphic variant at codon 109 of p27 gene may not be a marker for determining patients' risk of developing breast cancer but it may be a potential genetic marker for poor prognosis, thereby a marker for tumor prognosis.
The HER2 codon Ile655Val and Cyclin D1 (CCND1) G870A polymorphisms were analyzed in a hospital-based Malaysian population using PCR-RFLP method. Peripheral blood samples were collected from 230 breast cancer patients, and 200 normal and healthy women who had no history of breast disease or breast cancer. We evaluated the association between HER2 or CCND1 polymorphisms and breast cancer risk, and clinico-pathological parameters in the population. The genotype and allele frequencies of HER2 (P=0.163 vs P=0.0622) and CCND1 (P=0.377 vs P=0.284) polymorphisms were not significantly different between the breast cancer cases and normal subjects, respectively. Women who were Ile/Val heterozygotes (OR=1.48; 95% CI, 0.91-2.43), Val/Val homozygotes (OR=1.93; 95% CI, 0.51-7.77) and carriers of Val allele genotype (OR=1.53; 95% CI, 0.95-2.45) were not significantly associated with increased breast cancer risk. Similarly, women who were homozygous (OR=1.34; 95% CI, 0.77-2.34) or heterozygous (OR=0.98; 95% CI, 0.60-1.60) for A allele, or carriers of A allele genotype (OR=1.10; 95% CI, 0.70-1.73) were not associated with breast cancer risk. Analysis on clinico-pathological parameters showed that Val allele genotype was significantly correlated with nodal metastases but A allele genotype was not associated with any of the variables. Our findings suggest that the polymorphic alleles of HER2 and CCND1 may not play an important role as genetic markers for breast cancer risk, but presence of Val allele may be useful for tumor prognosis.
BACKGROUND: Breast cancer is the commonest cancer amongst Malaysian women but local survival data are scarce. The present study was therefore conducted to assess overall survival and prognostic factors in Malaysian breast cancer patients.
METHODS: The research sample was a prospective cohort of 413 patients diagnosed with breast cancer in the University of Malaya Medical Centre between 1993 to 1997. Survival data were obtained from the National Registry of Birth and Deaths in December 2000. The clinico-pathological variables studied were age, ethnic group, stage, tumour size, lymph node status, oestrogen receptor status and grade. The data were analysed utilizing Splus statistical software. The important prognostic factors were identified by fitting the Cox's proportional hazard model to the data set. Survival probabilities were estimated using the Kaplan-Meier method and differences were compared by the log-rank test.
RESULTS: The overall 5-year survival was 59.1%. The Cox's proportional hazard model identified stage, lymph node status, size and grade as factors that correlated with prognosis. Age was not a significant prognostic factor. The Cox regression model by stepwise selection showed stage, nodal status and grade of tumour to be independent prognostic factors, whereas ethnicity, age and ER status were not.
INTERPRETATION: The overall survival in our centre was low. Recognizing factors that affect prognosis of breast cancer patients in Malaysia may improve delivery of health care to at-risk groups by strategizing interventions as survival depends on early detection and effective treatment.