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.

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.

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.

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.

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.

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.

The Will Rogers phenomenon in the staging of breast cancer - does it matter?

INTRODUCTION: Changes in the American Joint Commission on Cancer staging for breast cancer occurred when the 5th Edition was updated to the 6th Edition. OBJECTIVE: To investigate how these changes affected stage and survival. METHODS: 3127 cases of breast cancer were restaged. RESULTS: Late stages increased from 27.7% to 38.1%. The five-year survival improved in Stage 2 (82.9-86.1%) and Stage 3 (50.6-59%). DISCUSSION: Stage shift leads to an erroneous impression that women are presenting with later stages and stage-specific survival is improving. CONCLUSION: Standardizing cancer staging is important when reporting stage and survival in different time periods.

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.

Audit of birth defects in 34,109 deliveries in a tertiary referral center.

The objective of the study is to determine the proportion and different types of birth defects among the children born in Hospital Kuala Lumpur. A cross-sectional study was conducted for a period of 18 months where all consecutively born infants, dead or alive were included. There were total of 34,109 births recorded during this period. The proportion of birth defects in Hospital Kuala Lumpur was 3.1% (n = 1056). The commonest involved were the hematology system, (157.7 per 10,000 births), the central nervous system, genitourinary system and chromosomal anomalies. The proportion was significantly higher in males and in the Chinese (p < 0.001). The commonest abnormalities are Glucose 6 Phosphate Deficiency (157.7/10000), Down's syndrome (12.6/10000), thalassaemia (8.8/10000), cleft lip and/or palate (7.6/10000) and anencephaly (7.3/10000). Neural tube defect is common and ranked second after G6PD deficiency. There is a need for a birth defect registry to assess the extent of the problem in Malaysia.