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Malaysia is a developing country made up of three main ethnicities: Malay, Chinese and Indian. There are significant ethnic differences with regard to the type of daily food and cooking methods, contraception, breast-feeding preferences, confinement period and care, postmenopausal intake and influence of the traditional healer. Breast cancer is the most common cancer among Malaysian women across all three ethnicities. However, the National Cancer Registry and local medical centres have documented ethnic differences in breast cancer risk (Chinese, 40.7 per 100,000; Indian, 38.1 per 100,000; Malay, 31.5 per 100,000), peak age (youngest in the Malays), stage at presentation (largest percentage at advanced stage among the Malays) and survival (poorest survival rate among the Malays). The Malays have several practices that are protective against breast cancer compared with the Chinese. However, the Malays have strong beliefs in the traditional healer, which contribute to the delay in getting treatment, causing a poor outcome and a low survival rate. The highest BRCA1 and 2 genetic mutation incidence is amongst the Chinese, but the Malays have the largest triple-negative breast cancer rates. These factors may also contribute to the statistical breast cancer data.

Background Quality of life (QoL) is one of the treatment outcome measures in patients with breast cancer. In this study, we measured the QoL of women with breast cancer at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and identified the associated factors. Methodology This cross-sectional study was conducted from October 2017 to December 2017 and involved female patients with breast cancer. The QoL scores and domains were determined using the EuroQol EQ-5D-5L, and were presented as the utility value and visual analog scores, respectively. Results We recruited a total of 173 women, aged 33–87 years. The median VA score was 80.00 (interquartile range [IQR] 70.00–90.00); the median utility value was 0.78 (interquartile range [IQR] 0.65–1.00. Women who did not take traditional medicine had a higher utility index score of 0.092 (95% CI 0.014–0.171), and women with household income of RM3000–5000 had a higher utility index score of 0.096 (95% CI 0.011–0.180). Conclusion Traditional medicine consumption and household income were significantly associated with lower QoL. The pain/discomfort domain was the worst affected QoL domain and was related to traditional medicine use and household income. Addressing pain management in patients with breast cancer and the other factors contributing to lower QoL may improve the QoL of breast cancer survivors in the future.

Yong Hui Nies,1 Adliah Mhd Ali,1 Norlia Abdullah,2 Farida Islahudin,1 Noraida Mohamed Shah1 1Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Department of Surgery, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia Purpose: The objective of this study was to explore the experiences and side-effects of breast cancer patients on chemotherapy in Malaysia. Participants and methods: Purposive sampling of 36 breast cancer patients who have completed chemotherapy and agreed to participate in semi-structured in-depth interviews. A constant comparative method and thematic analysis were used to analyze the interviews. Results: Data were categorized into six main themes: know nothing of chemotherapy; fear of chemotherapy; patients’ beliefs in alternative treatments; symptom management; staying healthy after chemotherapy; and concerns of patients after chemotherapy. Conclusion: Despite complaints about the bad experiences of their chemotherapy-induced side-effects, these patients still managed to complete the entire course of chemotherapy. Moreover, there is a need for a clinical pharmacy service in the oncology clinic setting in Malaysia in order to provide relevant information to help patients understand the chemotherapy received. Keywords: breast cancer, chemotherapy, clinical pharmacy service, Malaysia, semi-structured interview

Yong Hui Nies,1 Farida Islahudin,1 Wei Wen Chong,1 Norlia Abdullah,2 Fuad Ismail,3 Ros Suzanna Ahmad Bustamam,4 Yoke Fui Wong,5 JJ Saladina,2 Noraida Mohamed Shah1 1Faculty of Pharmacy, 2Department of Surgery, 3Department of Radiotherapy and Oncology, Universiti Kebangsaan Malaysia Medical Centre, 4Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Kuala Lumpur, 5Department of Radiotherapy and Oncology, National Cancer Institute, Putrajaya, Malaysia Purpose: This study investigated breast cancer patients’ involvement level in the treatment decision-making process and the concordance between patients’ and physician’s perspectives in decision-making. Participants and methods: A cross-sectional study was conducted involving physicians and newly diagnosed breast cancer patients from three public/teaching hospitals in Malaysia. The Control Preference Scale (CPS) was administered to patients and physicians, and the Krantz Health Opinion Survey (KHOS) was completed by the patients alone. Binary logistic regression was used to determine the association between sociodemographic characteristics, the patients’ involvement in treatment decision-making, and patients’ preference for behavioral involvement and information related to their disease. Results: The majority of patients preferred to share decision-making with their physicians (47.5%), while the second largest group preferred being passive (42.6%) and a small number preferred being active (9.8%). However, the physicians perceived that the majority of patients preferred active decision-making (56.9%), followed by those who desired shared decision-making (32.8%), and those who preferred passive decision-making (10.3%). The overall concordance was 26.5% (54 of 204 patient–physician dyads). The median of preference for information score and behavioral involvement score was 4 (interquartile range [IQR] =3–5) and 2 (IQR =2–3), respectively. In univariate analysis, the ethnicity and educational qualification of patients were significantly associated with the patients’ preferred role in the process of treatment decision-making and the patients’ preference for information seeking (p

Luminal breast cancer subtype (ER/PR+, HER2+/-) represents about two-thirds of all breast cancers, and better understanding of the genetic alterations underpinning the disease pathogenesis is desirable to develop improved treatment plans and to increase patients’ survival. To date, other than hormonal and anti-HER2 therapies (e.g. tamoxifen, aromatase inhibitor, trastuzumab), no other targeted therapies have been approved by FDA for luminal breast cancer. Despite thousands of breast tumour samples have been sequenced, there is no data yet on Malaysian patients. Therefore, it is clinically important to identify actionable mutated genes or pathways implicated in our local breast cancer patients to establish a more defined framework for precision medicine and clinical trials. In this discovery study, a total of nine pairs of newly diagnosed luminal breast cancer cases (>80% tumour content) and their matched normal samples were subjected to exome sequencing. We detected a total of 491 somatic from nine pairs of breast tumour-normal samples. PIK3CA is the most frequently mutated gene in our discovery cohort of patients (n=4/9). Kinases and phosphatases were found as the most significantly enriched mutated genes (enrichment score = 3.12), with all nine luminal breast cancer samples harboring at least one non-synonymous mutation in this cluster of genes. This profile suggested that alteration in protein phosphorylation processes is among the key drivers in luminal breast cancer pathogenesis. Interestingly, genes involved in four key druggable cancer pathways, i.e. PI3K/AKT/mTOR, MAPK/ERK, NF-kβ and VEGF signalling pathways were found commonly mutated and require validation in a larger cohort. In conclusion, we have successfully profiled the somatic mutations in Malaysian luminal breast cancer and this is the first study conducted in Malaysian patients. These findings revealed the role of multiple gene testing in discovering luminal breast cancer mutational landscape.

This study was conducted to determine the prevalence and severity of menopausal symptoms and their associated risk factors among postmenopausal breast cancer patients receiving adjuvant endocrine therapy.Postmenopausal breast cancer patients on endocrine therapy were recruited at three hospitals in Malaysia. Presence and severity of menopausal symptoms were determined using the Menopause Rating Scale. Sociodemographic and clinical data were collected from medical records.A total of 192 patients participated in this study. Commonly reported symptoms were musculoskeletal pain (59.9%), physical and mental exhaustion (59.4%), and hot flushes (41.1%). Multivariate analyses indicated that increasing number of years after menopause until the start of endocrine therapy was significantly associated with less likelihood of reporting menopausal symptoms and musculoskeletal pain. Patients with primary or secondary education levels reported significantly less menopausal urogenital symptoms compared to patients with a tertiary education level. Patients using aromatase inhibitors were twice as likely to experience musculoskeletal pain compared to patients using tamoxifen (odds ratio, 2.18; 95% confidence interval, 1.06-4.50; p 0.05).Menopausal symptoms and musculoskeletal pain are common problems encountered by postmenopausal breast cancer patients receiving adjuvant endocrine therapy and should be closely monitored for successful treatment.

There have been many DNA methylation studies on breast cancer which showed various methylation patterns involving tumour suppressor genes and oncogenes but only a few of those studies link the methylation data with gene expression. More data are required especially from the Asian region and to analyse how the epigenome data correlate with the transcriptome. DNA methylation profiling was carried out on 76 fresh frozen primary breast tumour tissues and 25 adjacent non-cancerous breast tissues using the Illumina Infinium(®) HumanMethylation27 BeadChip. Validation of methylation results was performed on 7 genes using either MS-MLPA or MS-qPCR. Gene expression profiling was done on 15 breast tumours and 5 adjacent non-cancerous breast tissues using the Affymetrix GeneChip(®) Human Gene 1.0 ST array. The overlapping genes between DNA methylation and gene expression datasets were further mapped to the KEGG database to identify the molecular pathways that linked these genes together. Supervised hierarchical cluster analysis revealed 1,389 hypermethylated CpG sites and 22 hypomethylated CpG sites in cancer compared to the normal samples. Gene expression microarray analysis using a fold-change of at least 1.5 and a false discovery rate (FDR) at p>0.05 identified 404 upregulated and 463 downregulated genes in cancer samples. Integration of both datasets identified 51 genes with hypermethylation with low expression (negative association) and 13 genes with hypermethylation with high expression (positive association). Most of the overlapping genes belong to the focal adhesion and extracellular matrix-receptor interaction that play important roles in breast carcinogenesis. The present study displayed the value of using multiple datasets in the same set of tissues and how the integrative analysis can create a list of well-focused genes as well as to show the correlation between epigenetic changes and gene expression. These gene signatures can help us understand the epigenetic regulation of gene expression and could be potential targets for therapeutic intervention in the future.

The human skeleton is the most common organ to be affected by metastatic cancer and bone metastases are a major cause of cancer morbidity. The five most frequent cancers in Malaysia among males includes prostate whereas breast cancer is among those in females, both being associated with skeletal lesions. Bone metastases weaken bone structure, causing a range of symptoms and complications thus developing skeletal-related events (SRE). Patients with SRE may require palliative radiotherapy or surgery to bone for pain, having hypercalcaemia, pathologic fractures, and spinal cord compression. These complications contribute to a decline in patient health- related quality of life. The multidimensional assessment of health-related quality of life for those patients is important other than considering a beneficial treatment impact on patient survival, since the side effects of treatment and disease symptoms can significantly impact health-related quality of life. Cancer treatment could contribute to significant financial implications for the healthcare system. Therefore, it is essential to assess the health-related quality of life and treatment cost, among prostate and breast cancer patients in countries like Malaysia to rationalized cost-effective way for budget allocation or utilization of health care resources, hence helping in providing more personalized treatment for cancer patients.

Background: HER-2/neu is a proto-oncogene that encodes a transmembrane tyrosine kinase growth factor which is crucial for stimulating growth and cellular motility. Overexpression of HER-2/neu is observed in 10-35% of human breast cancers and is associated with pathogenesis, prognosis as well as response to therapy. Given the imperative role of HER-2/neu overexpression in breast cancer, it is important to determine the magnitude of amplification which may facilitate a better prognosis as well as personalized therapy in affected patients. In this study, we determined HER-2/neu protein expression by immunohistochemistry (IHC) concurrently with HER-2/neu DNA amplification by quantitative real time-polymerase chain reaction (Q-PCR). Materials and Methods: A total of 53 paired tissue samples from breast cancer patients were frozen-sectioned to characterize the tumour and normal tissues. Only tissues with 80% tumour cells were used in this study. For confirmation, Q-PCR was used to determine the HER-2/neu DNA amplification. Results: We found 20/53 (37.7%) of the tumour tissues to be positive for HER-2/neu protein overexpression using IHC. Out of these twenty, only 9/53 (17%) cases were in agreement with the Q-PCR results. The concordance rate between IHC and Q-PCR was 79.3%. Approximately 20.7% of positive IHC cases showed no HER-2/neu gene amplification using Q-PCR. Conclusion: In conclusion, IHC can be used as an initial screening method for detection of the HER-2/neu protein overexpression. Techniques such as Q-PCR should be employed to verify the IHC results for uncertain cases as well as determination of HER-2/neu gene amplification

Genomic and transcriptomic alterations that affect cellular processes, such as cell proliferation, differentiation, apoptosis and invasion, commonly occur in breast oncogenesis. Epidemiological evidence has proven that the risk of breast cancer predisposition varies among different ethnicities. This study aims to identify the transcriptome changes that commonly occur during the transition of normal breast epithelium to carcinoma in three local ethnic groups (Malays, Chinese and Indians). The gene expression patterns of 43 breast carcinomas with 43 patient-matched normal breast tissues were investigated using Affymetrix U133A GeneChip (containing 22,283 probe sets targeting approximately 18,400 different transcripts) and analyzed with GeneSpring GX10. Our findings revealed a total of 33 significantly differentially expressed genes, which showed>2-fold change at a 99.9% confidence interval level (p

Background Addressing breast cancer patients’ unmet supportive care needs in the early stage of their survivorship have become a prime concern because of its significant association with poor quality of life (QOL), which in turn increases healthcare utilization and costs. There is no study about unmet supportive care needs of breast cancer patients in Malaysia. This study aims to assess the most prevalent unmet supportive care needs of Malaysian breast cancer patients and the association between QOL and patients’ characteristics, and their unmet supportive care needs. Methods A cross-sectional study was conducted at the Surgery and Oncology Clinic between May 2014 and June 2014 in a tertiary hospital in Malaysia. A total of 117 patients out of 133 breast cancer patients recruited by universal sampling were interviewed using a structured questionnaire consisted of three parts: participants’ socio-demographic and disease characteristics, Supportive Care Needs Survey-Short Form Questionnaire (SCNS-SF34) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Results The highest unmet supportive care needs were observed in the psychological domain (Mean 53.31; SD ± 21.79), followed by physical domain (Mean 38.16; SD ± 27.15). Most prevalent unmet supportive care needs were uncertainty about the future (78.6 %), fears about the cancer spreading (76.1 %), feelings of sadness (69.2 %), feelings about death and dying (68.4 %), concerns about those close to the patient (65.0 %) and feeling down or depressed (65.0 %). Multivariate linear analysis showed that early breast cancer survivors diagnosed at an advanced stage and with greater physical and psychological needs were significantly (p

Portable ultrasound is now used in a variety of clinical settings by specialties outside of radiology. Despite increased accessibility to ultrasound, the overall performance of ultrasound by breast surgeons is consistently low. We discuss the reasons why this is unacceptable for future patient care and answer the question, ‘Why should breast surgeons use ultrasound?’ We reviewed the literature for evidence assessing the outcomes of breast surgeon-performed ultrasound both intra-operatively and in the outpatient department. Intra-operative ultrasound performed by surgeons reduces re-excision rates in breast-conserving surgery. Outpatient-based ultrasound performed by surgeons frees up the resources of radiology departments, allowing them to focus upon patients requiring more complex diagnostic and interventional procedures. For surgeons to competently perform intra-operative and outpatient-based ultrasound, a period of formal ultrasound training is necessary to acquire knowledge of ultrasound skills and techniques. This should be followed by a period of mentorship and supervised training with an experienced breast radiologist. Breast surgeon-performed ultrasound is beneficial to the multi-disciplinary care of breast cancer patients. To further improve multidisciplinary care, breast surgeons and radiologists should work more collaboratively to optimise imaging applications both in the operating theatre and outpatient department. Current advances in therapeutic percutaneous techniques are of interest to both surgeons and radiologists. In future, a hybrid specialisation should be considered to incorporate accreditation in both specialties for breast interventional procedures.

The GATA3 gene is a potential tumour marker and putative tumour suppressor gene in breast cancer. Its expression is associated with better prognosis and disease free survival in breast cancer patients. We aimed to evaluate GATA3 transcriptome expression and mutation in breast carcinomas and correlate its expression with oestrogen receptor (ER), progesterone receptor (PR), lymph node (LN) status, tumour grade and c-erbB-2 expression. Twenty-two breast infiltrating ductal carcinomas and paired normal tissues were used in Branch DNA assay to detect GATA3 mRNA expression. Normalized data for GATA3 mRNA expression were grouped according to the ER, PR and LN status, tumour grade and c-erbB-2 expression of the tumours. Statistical significance was tested using t-test and ANOVA at 95% confidence interval level. Mutational analysis of GATA3 was performed by direct sequencing of the coding regions of GATA3 mRNA. Our findings showed that GATA3 gene were over-expressed and under-expressed by2 fold change in 12 and 4 tested samples, respectively. Eighty per cent of ER positive breast carcinomas were GATA3 positive. There was a statistically significant correlation between GATA3 expression and ER at 95% confidence interval level between the study groups. On the contrary, GATA3 expression was not statistically significant with PR, LN, tumour grade and c-erbB-2 expression in our study. In addition, we observed that there was no mutation in mRNA coding region in 16 breast carcinomas that showed GATA3 differential gene expression. Our preliminary results suggested that GATA3 is linked to the ER. This scenario suggests that GATA3 may play a crucial role in oestrogen receptor positive breast cancer patients. Whether GATA3 expression is involved in regulating tumour cell growth in oestrogen responsive breast cancer is a key question that remains to be answered.

Objective To assess ultrasonographically (US) guided needle aspirationof breast abscesses as an alternative to surgical incision and drainage. Methods In our prospective study, 30 patients with 31 breast abscesses (one patient had bilateral breast abscess) underwent percutaneous breast abscess drainage under US guidance with local anaesthesia and oral antibiotics between 1 January 2004 and 31 March 2005. These patients consisted of 16 (53.3%) nonlactating and 14 (46.7%) lactating women, with ages ranging from 18 to 68 years (median, 28 years). The racial distribution comprised 26 (86.7%) Malays, three (10%) Chinese and one (3.3%) Indian. All patients had the chief complaint of breast swelling and 25 (83.3%) had breast pain. Clinically, 28 (93.3%) were found to have a palpable mass. Nine (30%) lesions were in the upper outer quadrant of the left breast. US diameters ranged from 1 to 15 cm (median, 4 cm). The pus volumes varied from 1 to 200 mL (median, 14 mL). Results Fifteen (50%) patients required only a single aspiration, 10 required multiple aspirations and five required incision and drainage. Those patients in whom needle aspiration failed had multiloculated lesions irrespective of abscess volume and size. Conclusion Needle aspiration with ultrasound guidance is an effective treatment for breast abscess irrespective of abscess volume and size.

Aims . Clinical assessment of tumour size is often used to choose between mastectomy and primary medical therapy. Clinical and imaging modalities may have varying levels of accuracy across the range of tumour sizes. The aim of this study was to compare the accuracy of clinical measurement and ultrasound in discriminating palpable tumours up to 3 cm vs those greater than 3 cm. Methods . A prospective analysis of 111 consecutive patients with palpable breast cancer was performed. All women had clinical measurement by caliper and ultrasound assessment prior to any needle biopsy. Clinical measurement and ultrasound assessment of size were compared to pathological tumour size of the surgical specimen. Results . Both clinical and ultrasound measurement underestimate the size of larger tumours. The overall accuracy of clinical assessment and ultrasound examination in correctly identifying a 30 mm cut off was 70.3 and 77.5%, respectively. Ultrasound was significantly more accurate at determining the size of tumours p =0.007) but there was no significant difference between both modalities in assessing tumours greater than 30 mm. Conclusions . Ultrasound assessment of breast cancer size is more accurate than clinical assessment for tumours less than 30 mm. As clinical examination is as accurate on ultrasound for tumours greater than 30 mm, clinical assessment of tumour size alone is adequate to select patients for primary medical therapy or mastectomy.

The amount of breast tissue within the inframammary fold (IMF) is controversial. Preservation of the IMF during mastectomy facilitates breast reconstruction and led some surgeons to practice conservation of the IMF, contrary to traditional descriptions of total mastectomy. The aim of this study was to analyse the clinical significance of IMF tissue content. A total of 50 IMF specimens were studied from 42 patients who underwent mastectomy between January 2001 and December 2002. The amount of breast tissue within each IMF was evaluated. The median patient age was 46 (range 33-86) years. The median body mass index was 23.4 (18.1-38.3)kg/m(2). The median IMF volume resected was 2 (0.2-9.7)cm(3) which was 0.6 (0.1-2.0)% of the breast volume. Ten specimens (20%) contained breast tissue and one (2%) contained breast tissue and an inframammary lymph node. Three specimens (6%) containing fibrofatty tissue without breast parenchyma had intramammary lymph nodes within the IMF. One patient (2%) who had a mastectomy for invasive ductal carcinoma had IMF tissue containing a lymph node within the IMF with breast cancer metastasis. The presence of breast tissue or lymph nodes within the IMF was unrelated to patient age, body mass index, the amount of IMF tissue in relation to breast volume and absolute breast size. Our finding that breast tissue and intramammary lymph nodes are present in 28% of IMF specimens requires re-consideration of the safety of preserving the IMF at mastectomy. If IMF tissue is resected and the immediate breast reconstruction is performed, the superficial fascial system should be reconstructed after excision of the IMF tissue in order to recreate the inframammary crease.

Squamous cell carcinoma of the breast: clinico-pathologic implications and outcome. Aims: Pure squamous cell carcinoma (SCC) of the breast is a rare tumour and little is known about long-term outcome. We report our experience of a consecutive series of patients. Methods: All patients with SCC treated at our institution between 1970 and 2001 were included. The pathological features, outcome and prognosis were studied. Results: Eleven patients were identified. The median age was 55 (38-90) years and median follow-up was 62 (3-332) months. Four tumours were T1, three were T2 and three were T3 (one tumour size was unknown). There were seven poorly differentiated and three moderately differentiated SCC. Tumour grade could not be assessed in one patient. Primary treatment was mastectomy in six patients, wide local excision in four patients and radiotherapy in one patient. There was lymph node (LN) involvement in two patients. Oestrogen receptor status was assessed in seven patients and only one tumour was positive. Adjuvant chemotherapy was given to three patients and five patients received adjuvant radiotherapy. Two patients developed local recurrence at 5 and 12 months and three patients developed distant metastasis at 2, 36 and 306 months. Three patients were treated with chemotherapy at recurrence. Three patients have died of the disease, two are alive with disease and six remain well. The 2-and 5-year overall survival was 80% (SE = 13%) and 67% (SE = 16%) respectively. Large tumour size and positive LN status were prognostic indicators of poor outcome. Conclusion: SCC of the breast adopts an aggressive course with outcome comparable to poorly differentiated breast adenocarcinoma. (C) 2003 Elsevier Science Ltd. All rights reserved.