Global Disparities in Breast Cancer Genetics Testing, Counselling and Management.

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

Machine Learning and Deep Learning Approaches in Breast Cancer Survival Prediction Using Clinical Data.

Breast cancer survival prediction can have an extreme effect on selection of best treatment protocols. Many approaches such as statistical or machine learning models have been employed to predict the survival prospects of patients, but newer algorithms such as deep learning can be tested with the aim of improving the models and prediction accuracy. In this study, we used machine learning and deep learning approaches to predict breast cancer survival in 4,902 patient records from the University of Malaya Medical Centre Breast Cancer Registry. The results indicated that the multilayer perceptron (MLP), random forest (RF) and decision tree (DT) classifiers could predict survivorship, respectively, with 88.2 %, 83.3 % and 82.5 % accuracy in the tested samples. Support vector machine (SVM) came out to be lower with 80.5 %. In this study, tumour size turned out to be the most important feature for breast cancer survivability prediction. Both deep learning and machine learning methods produce desirable prediction accuracy, but other factors such as parameter configurations and data transformations affect the accuracy of the predictive model.

Low Lifetime Risk of Contralateral Breast Cancer in a Middle-Income Asian Country: Evidence to Guide Post-treatment Surveillance.

BACKGROUND: The rate of contralateral risk-reducing mastectomy (CRRM) is increasing in the West with controversial evidence of improved survival in early breast cancer patients. Although uptake of CRRM in Asia appears low, the trends may rise, and there is currently an urgent need to provide evidence for informed decision-making in clinical practice. This study aims to determine the risk of contralateral breast cancer (CBC) and its associated factors in an Asian setting. METHOD: A total of 2937 newly diagnosed patients with stage I and stage II breast cancer in University Malaya Medical Centre between Jan 1993 to Dec 2012 were included in the study. Multinomial logistic regression analysis allowing death to compete with CBC as a study outcome was used; patients with unilateral breast cancer who were alive were taken as reference. A stepwise backward regression analysis including age at diagnosis, ethnicity, family history of breast cancer, TNM stage, hormonal receptor status, HER2 status, chemotherapy, radiotherapy, and hormone therapy was conducted. RESULTS: Fifty women developed CBC, over a median follow-up of 6 years. The 5- and 10-year cumulative risk of contralateral breast cancer was 1.0% (95% CI 0.6-1.4%) and 2.8% (95% CI 2.0-3.6%), respectively. Young age at diagnosis of first cancer, positive family history, and stage I disease were independent predictors of CBC. DISCUSSION: The current study suggests that the risk of CBC is very low in a Southeast Asian setting. Any recommendations or practice of CRRM should be reviewed with caution and patients must be counseled appropriately.

Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing.

Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.

Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer.

BACKGROUND: Peripheral blood-derived inflammation-based scores such as the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer. METHODS: Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR. RESULTS: Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6-82.1%) in quintile 1, 79.4% (95% CI: 74.4-83.7%) in quintile 2, 72.1% (95% CI: 66.3-77.3%) in quintile 3, 65.6% (95% CI: 59.8-70.8%) in quintile 4 and 51.1% (95% CI: 43.3-58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08-1.63); Ptrend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9-59.2%) vs 77.0% (95% CI: 70.9-82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04-1.52). CONCLUSIONS: Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.

Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country.

INTRODUCTION: Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes. OBJECTIVE: To compare the clinicopathological features and survival of ER and/or PR positive HER2 negative (ER+PR+HER2-, ER+PR-HER2- or ER-PR+HER2-), ER and/or PR positive HER2 positive (ER+PR+HER2+, ER+PR-HER2+ or ER-PR+HER2+), ER negative PR negative HER2 positive (ER-PR-HER2+), and ER negative PR negative HER2 negative (ER-PR-HER2-) subtypes. METHODS: 1957 patients with Stage 1-3 breast carcinoma diagnosed between Jan 2005 and Dec 2011 were categorized into the four subtypes. The clinicopathological features between the subtypes were compared using χ (2) test. Kaplan-Meier analysis was performed to estimate 5-year overall survival. Multivariate Cox regression was used to determine the association between subtypes and mortality adjusted for age, ethnicity, stage, pathological features, and treatment. RESULTS: ER-PR-HER2+ and ER-PR-HER2- subtypes were associated with younger age, larger tumors, and higher grade. There was no difference in the 5-year survival of the ER-PR-HER2+ and ER-PR-HER2- subtypes (75.1 and 74.4 %, respectively) and survival was poorer than in the ER and/or PR positive HER2 negative and ER and/or PR positive HER2 positive subtypes (87.1 and 83.1 %, respectively). Only 9.5 % of women with HER2 positive breast cancer had access to trastuzumab. CONCLUSION: In a low resource setting with limited access to trastuzumab, there is no difference in survival between the ER-PR-HER2+ and ER-PR-HER2- subtypes of breast cancer.

Spectrum of very early breast cancer in a setting without organised screening.

BACKGROUND: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined. METHODS: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings. RESULTS: Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6-99.6%). CONCLUSIONS: The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.

Incidence of chemotherapy-induced ovarian failure in premenopausal women undergoing chemotherapy for breast cancer.

INTRODUCTION: Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients. OBJECTIVE: This study's aim was to find the incidence of chemotherapy-induced ovarian failure (CIOF) and reversible amenorrhea in premenopausal non-metastatic breast cancer patients. METHOD: This mixed retrospective and prospective study follows premenopausal breast cancer patients receiving chemotherapy between 2008 and 2012. Patients in the prospective arm were followed up with menstrual history and serum ovarian hormones (follicle-stimulating hormone [FSH] and estradiol) until 1 year post-chemotherapy, and patients in the retrospective arm were contacted for their menstrual history. RESULTS: The mean age of the 102 subjects was 43.3 years. Of the patients, 93.1 and 77.9 % were amenorrheic at completion of chemotherapy and at 12 months post-chemotherapy, respectively. Of those who developed amenorrhea, 24.6 % regained menstruation, on average after 7.86 (range 1-15) months post-chemotherapy. Age was the only statistically significant risk factor. CIOF and reversible amenorrhea was 57 and 50 % at <35 years, 95 and 31.6 % at 35-45 years, and 97.9 and 14.9 % at >50 years, respectively. The 33 prospective patients' estradiol and FSH levels seem to correlate well with onset of amenorrhea, with a falling estradiol and rising FSH trend. Tamoxifen use was associated with elevated estradiol levels 1 year post-chemotherapy. CONCLUSION: This study found a high incidence of CIOF, with a relatively low rate of reversible amenorrhea. Premenopausal patients should be counselled prior to treatment and education and support provided.

Prediction of lymph node involvement in patients with breast tumors measuring 3-5 cm in a middle-income setting: the role of CancerMath.

BACKGROUND: In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases. OBJECTIVE: We investigated whether CancerMath, a free online prediction tool for axillary lymph node involvement, is able to identify women at low risk of axillary lymph node metastases in Malaysian women with 3-5 cm tumors, with the aim to offer SNB in a targeted, cost-effective way. METHODS: Women with non-metastatic breast cancers, measuring 3-5 cm were identified within the University Malaya Medical Centre (UMMC) breast cancer registry. We compared CancerMath-predicted probabilities of lymph node involvement between women with versus without lymph node metastases. The discriminative performance of CancerMath was tested using receiver operating characteristic (ROC) analysis. RESULTS: Out of 1,017 patients, 520 (51 %) had axillary involvement. Tumors of women with axillary involvement were more often estrogen-receptor positive, progesterone-receptor positive, and human epidermal growth factor receptor (HER)-2 positive. The mean CancerMath score was higher in women with axillary involvement than in those without (53.5 vs. 51.3, p = 0.001). In terms of discrimination, CancerMath performed poorly, with an area under the ROC curve of 0.553 (95 % confidence interval CI 0.518-0.588). Attempts to optimize the CancerMath model by adding ethnicity and HER2 to the model did not improve discriminatory performance. CONCLUSION: For Malaysian women with tumors measuring 3-5 cm, CancerMath is unable to accurately predict lymph node involvement and is therefore not helpful in the identification of women at low risk of node-positive disease who could benefit from SNB.

Breast health in developing countries.

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.

Impact of breast surgery on survival in women presenting with metastatic breast cancer.

BACKGROUND: Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated. METHODS: Women presenting with metastatic breast cancer at the initial diagnosis at the University Malaya Medical Centre (Malaysia) between 1993 and 2008 were included in the study. Mortality of patients who had primary breast surgery was compared with that of those without surgery, and adjusted for possible confounders by means of a propensity score. RESULTS: Of 3689 patients, 375 (10·2 per cent) presented with metastatic disease. One hundred and thirty-nine patients (37·1 per cent) underwent surgery. A total of 330 deaths occurred during 6814 person-months of follow-up. The 2-year survival rate was 21·2 (95 per cent confidence interval (c.i.) 15·9 to 26·5) per cent in women who did not have surgery and 46·3 (37·7 to 54·9) per cent in those who had breast surgery. Breast surgery was associated with a 28 per cent lower risk of death (hazard ratio 0·72, 95 per cent c.i. 0·56 to 0·94), after adjustment for patient and tumour characteristics, metastatic profile and treatment. CONCLUSION: Surgical resection of the primary breast tumour was independently associated with a survival advantage in patients presenting with metastatic breast cancer.

Polymorphism of FGFR4 Gly388Arg does not confer an increased risk to breast cancer development.

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.

Clinical and pathologic differences between BRCA1-, BRCA2-, and non-BRCA-associated breast cancers in a multiracial developing country.

BACKGROUND: Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population. METHODS: We conducted a retrospective review of the medical records of 152 women with breast cancer who underwent genetic testing for BRCA mutations. The patients self-reported ethnicity, age at onset, and clinical stage at diagnosis and tumor pathology were reviewed. RESULTS: A total of 31 patients carried germline deleterious mutations (16 BRCA1, 15 BRCA2). We found that tumors in BRCA1 carriers were more likely to be estrogen receptor (ER)-negative and progesterone receptor (PR)-negative. HER2 was more likely to be negative in both BRCA1 and BRCA2 subjects compared with non-BRCA subjects. We found a strong association between triple-negative status and BRCA1 carriers. In addition, tumors in BRCA1 carriers were more likely to be higher grade than those in BRCA2 and non-BRCA carriers; but the difference was not statistically significant. CONCLUSIONS: These results suggest that tumors associated with BRCA1 mutations are distinct from those of BRCA2-associated and non-BRCA-associated breast cancers, and that the tumors associated with BRCA2 mutations are similar to the non-BRCA-associated breast cancers. Further studies are required to determine if the prognosis is different in each of these groups and the best management strategy for each group.

Associations between hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms and risk of developing breast cancer.

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.

Total parathyroidectomy under local anaesthesia for renal hyperparathyroidism.

INTRODUCTION: Renal hyperparathyroidism with attendant osteodystrophy is a frequent and severe morbidity affecting the quality of life of end stage renal failure patients surviving on long-term renal replacement therapy. A small subgroup of these patients with severe cardiorespiratory dysfunction was deemed at very high risk for general anaesthesia (GA). We report on a series of total parathyroidectomy under local anaesthesia (LA) for these patients. METHODOLOGY: A total of 32 consecutive patients with severe cardiorespiratory dysfunction who underwent total parathyroidectomy under LA over a period of 7 years were prospectively accrued in this study. The patient characteristics, the operative outcome and the feasibility to surgery under LA were analysed. RESULTS: Sixteen of the patients (50%) had severe restrictive lung disease as a result of renal osteodystrophy and the other 16 patients had poor cardiac status. Histopathological examination confirmed 23 (71.9%) patients had four glands removed and seven (21.9%) patients had three glands removed. Two patients had only two glands removed and had recurrent hypercalcaemia. However, all patients reported symptomatic improvement. The post-operative complications were minimal; one patient had acute coronary syndrome and wound haematoma and another patient had wound haematoma which necessitated exploration under LA. A further patient developed congestive heart failure requiring treatment in the coronary care unit. CONCLUSION: Total parathyroidectomy can be performed safely and successfully under LA. We believe surgery under LA would be the most appropriate option for selected, high-risk patients to minimise the risk of GA.

Evaluation of Ge-doped silica fibre TLDs for in vivo dosimetry during intraoperative radiotherapy.

Ge-doped silica fibre (GDSF) thermoluminescence dosimeters (TLD) are non-hygroscopic spatially high-resolution radiation sensors with demonstrated potential for radiotherapy dosimetry applications. The INTRABEAM® system with spherical applicators, one of a number of recent electronic brachytherapy sources designed for intraoperative radiotherapy (IORT), presents a representative challenging dosimetry situation, with a low keV photon beam and a desired rapid dose-rate fall-off close-up to the applicator surface. In this study, using the INTRABEAM® system, investigations were made into the potential application of GDSF TLDs for in vivo IORT dosimetry. The GDSFs were calibrated over the respective dose- and depth-range 1 to 20 Gy and 3 to 45 mm from the x-ray probe. The effect of different sizes of spherical applicator on TL response of the fibres was also investigated. The results show the GDSF TLDs to be applicable for IORT dose assessment, with the important incorporated correction for beam quality effects using different spherical applicator sizes. The total uncertainty in use of this type of GDSF for dosimetry has been found to range between 9.5% to 12.4%. Subsequent in vivo measurement of skin dose for three breast patients undergoing IORT were performed, the measured doses being below the tolerance level for acute radiation toxicity.

Low Breast Conserving Surgery (BCS) rates in public hospitals in Malaysia: The effect of stage and ethnicity.

INTRODUCTION: Breast-conserving surgery (BCS) with radiation therapy is the procedure of choice for early-stage breast cancer. Survival and locoregional recurrence is non-inferior to mastectomy, with superior cosmetic and psycho-social outcomes. Differing health systems have demonstrated a wide variation in the rate of BCS. Little is known about the rate of BCS and factors influencing its practice in middle resource countries. This study aims to examine the BCS rates in Malaysia and to identify factors influencing its uptake. METHODOLOGY: This is a multi-centre, cross-sectional study involving the University of Malaya Medical Centre (UMMC), Queen Elizabeth II Hospital (QEH), and Tengku Ampuan Rahimah Hospital (TARH). Patients diagnosed with invasive breast cancer from January 2014 to December 2015 were included, excluding stromal cancers and lymphomas. Univariate and multivariate analyses identified factors influencing BCS. RESULTS: A total of 1005 patients were diagnosed with breast cancer in the allocated time frame. Excluding incomplete records and those who did not have surgery, 730 patients were analysed. Overall BCS rate was 32.9%. The BCS rate was highest at QEH (54.1%), followed by UMMC (29.5%), and TARH (17.4%). 16.9% had BCS after neoadjuvant therapy. Factors influencing BCS uptake included age, ethnic group, breast-surgeon led services, AJCC Stage, tumour size, HER-2 expression, and tumour grade. CONCLUSIONS: The rate of BCS in Malaysia is low. A wide variation of rate exists among the studied hospitals. Younger age, earlier AJCC stage, and the presence of a Breast sub-specialist surgeon, would make it more likely that the patient has her breast conserved.

Breast-conserving surgery versus mastectomy in young women with breast cancer in Asian settings.

Background: Mastectomy rates among women with early breast cancer in Asia have traditionally been high. This study assessed trends in the surgical management of young women with early-stage breast cancer in Asian settings. Survival in women treated with breast-conserving surgery (BCS; lumpectomy with adjuvant radiotherapy) and those undergoing mastectomy was compared. Methods: Young women (aged less than 50 years) newly diagnosed with stage I or II (T1-2 N0-1 M0) breast cancer in four hospitals in Malaysia, Singapore and Hong Kong in 1990-2012 were included. Overall survival (OS) was compared for patients treated by BCS and those who had a mastectomy. Propensity score analysis was used to account for differences in demographic, tumour and treatment characteristics between the groups. Results: Some 63·5 per cent of 3536 women underwent mastectomy. Over a 15-year period, only a modest increase in rates of BCS was observed. Although BCS was significantly associated with favourable prognostic features, OS was not significantly different for BCS and mastectomy; the 5-year OS rate was 94·9 (95 per cent c.i. 93·5 to 96·3) and 92·9 (91·7 to 94·1) per cent respectively. Inferences remained unchanged following propensity score analysis (hazard ratio for BCS versus mastectomy: 0·81, 95 per cent c.i. 0·64 to 1·03). Conclusion: The prevalence of young women with breast cancer treated by mastectomy remains high in Asian countries. Patients treated with BCS appear to survive as well as those undergoing mastectomy.

Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer.

INTRODUCTION: The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia. METHOD: A total of 187 breast cancer patients with either early-onset breast cancer (at age