Ava Kwong

Hong Kong Sanatorium & Hospital, Hong Kong, Hong Kong

Are you Ava Kwong?

Claim your profile

Publications (104)507.98 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain metastasis occurs in 10-15% of metastatic breast cancer patients and is associated with poor prognosis. This study aims to identify tumor characteristics of primary breast cancer, which are related to brain metastases in Hong Kong Chinese patients. A retrospective study of patients with invasive breast cancer receiving treatment in a university hospital from January 2001 to December 2008 was performed. The clinicopathological factors of patients with brain metastases were analyzed and compared with those who had no brain metastasis. Risk factors for brain metastasis were identified by univariate analysis first and then by multivariate analysis. A total of 912 patients with invasive breast cancer were treated during the study period. Of these, 30 patients were found to have distant metastases to brain. Patients with brain metastases had more breast tumors of higher histological grade (Grade III, 78.9% vs. 30.2%; p = 0.001). Their tumors also had a significantly higher rate of negative estrogen receptors (78.9% vs. 30.2%, p = 0.001). On multivariate analysis, only high tumor grading was found to be predictive of developing brain metastasis. Chinese breast cancer patients with brain metastasis were more likely to have high-grade tumors and negative estrogen receptor status. A more vigorous surveillance program for the central nervous system should be considered for this group of patients. Copyright © 2015. Published by Elsevier Taiwan.
    07/2015; DOI:10.1016/j.asjsur.2015.03.003
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 5%-10% of breast cancers are due to genetic predisposition caused by germline mutations; the most commonly tested genes are BRCA1 and BRCA2 mutations. Some mutations are unique to one family and others are recurrent; the spectrum of BRCA1/BRCA2 mutations varies depending on the geographical origins, populations or ethnic groups. In this review, we compiled data from 11 participating Asian countries (Bangladesh, Mainland China, Hong Kong SAR, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Thailand and Vietnam), and from ethnic Asians residing in Canada and the USA. We have additionally conducted a literature review to include other Asian countries mainly in Central and Western Asia. We present the current pathogenic mutation spectrum of BRCA1/BRCA2 genes in patients with breast cancer in various Asian populations. Understanding BRCA1/BRCA2 mutations in Asians will help provide better risk assessment and clinical management of breast cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Medical Genetics 07/2015; DOI:10.1136/jmedgenet-2015-103132 · 5.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A diagnosis of advanced breast cancer (ABC) challenges a woman's ambitions. This longitudinal study explored (1) if goal adjustment disposition influenced psychological adjustment patterns among women with ABC and (2) if dispositional hope and optimism moderate effects of goal adjustment on psychological adjustment. One hundred ninety three out of 225 women with ABC were assessed while they were awaiting/receiving initial chemotherapy, then again at 6 weeks, 3 months, 6 months, and 12 months post-baseline. Goal disengagement, goal reengagement, optimism, hope, and psychological adjustment (anxiety, depression, and positive affect) were assessed at baseline; psychological adjustment was reassessed at each follow-up. Latent growth curve modeling was used to examine the change of psychological adjustment and test the study objectives. High goal disengagement, low reengagement, and high optimism were associated with lower initial anxiety, while high goal disengagement and optimism predicted a slower rate of change in anxiety. High goal disengagement, reengagement, and optimism were associated with lower initial depression. High goal reengagement, optimism, and hope were associated with initial positive affect scores, while optimism predicted its rate of change. Optimism moderated the effect of goal disengagement on anxiety and depression, whereas hope moderated the effect of goal reengagement on positive affect. Goal disengagement and reengagement are two relatively independent processes influencing psychological well-being. These findings will help clinicians to tailor specific interventions to help women coping with the diagnosis of ABC. Copyright © 2015 John Wiley & Sons, Ltd.
    Psycho-Oncology 06/2015; DOI:10.1002/pon.3871 · 4.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer. Sanger sequencing has been the gold standard in identifying these mutations. However, 4-28% of inherited BRCA mutations may be due to large genomic rearrangements (LGRs), which could be missed by using Sanger sequencing alone. Our aim is to evaluate the pick-up rate of LGRs in our cohort. A total of 1,236 clinically high-risk patients with breast and/or ovarian cancers were recruited through The Hong Kong Hereditary Breast Cancer Family Registry from 2007 to 2014. Full gene sequencing (either Sanger or next generation sequencing) and multiplex ligation-dependent probe amplification (MLPA) were performed. We identified 120 deleterious BRCA mutations: 57 (4.61%) were in BRCA1 and 63 (5.10%) were in BRCA2. LGRs accounted for 6.67% (8 of 120) of all BRCA mutations, whereas 8.77 % (5 of 57) were BRCA1 mutations and 4.76% (3 of 63) were BRCA2 mutations. Through this integrated approach, both small nucleotide variations and LGRs could be detected. We suggest that MLPA should be incorporated into the standard practice for genetic testing to avoid false-negative results, which would greatly affect the management of these high-risk families. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cancer Genetics 06/2015; DOI:10.1016/j.cancergen.2015.05.031 · 2.42 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P3-07-32-P3-07-32. DOI:10.1158/1538-7445.SABCS14-P3-07-32 · 9.28 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):P2-07-07-P2-07-07. DOI:10.1158/1538-7445.SABCS14-P2-07-07 · 9.28 Impact Factor
  • V Y Shin · J M Siu · I Cheuk · E K O Ng · A Kwong
    [Show abstract] [Hide abstract]
    ABSTRACT: Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer in women globally. This subtype often has early and high recurrence rates resulting in poor survival, partially due to lack of targeted therapies. Therefore, there is an urgent need to identify TNBC-specific biomarkers for early diagnosis and treatment monitoring, and to develop more effective targeted therapy. By using miRCURY LNA array platform, we compared the differential miRNA expressions in plasma of patient with TNBC (n=5) and non-TNBC (n=5), as well as healthy controls (n=5). Potential miRNAs were then validated in a large cohort of patients by real-time PCR. Ten putative miRNAs from the microarray data that differentially expressed between non-TNBC and healthy controls were identified. In the screening phase (n=90), we selected five miRNAs (miR-92a-3p, miR-342-3p, miR-16, miR-21 and miR-199a-5p) that could discriminate TNBC from non-TNBC for further validation. Results showed that miR-16, miR-21 and miR-199a-5p were underexpressed in TNBC when compared with non-TNBC, and were further validated in a large cohort (n=252). In addition, post-operative plasma levels of miR-16, miR-21 and miR-199a-5p were significantly restored when compared with pre-operative plasma of TNBC. Plasma miR-199a-5p expression in TNBC had significant difference when compared with non-TNBC and healthy controls, the receiver-operator characteristics curve analysis revealed the highest area under curve (AUC=0.8838) among all. The expression levels were associated with TNM stage and tumour subtypes. Our data suggest that miR-199a-5p could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC.British Journal of Cancer advance online publication, 23 April 2015; doi:10.1038/bjc.2015.143 www.bjcancer.com.
    British Journal of Cancer 04/2015; 112(11). DOI:10.1038/bjc.2015.143 · 4.82 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IMPORTANCE: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. OBJECTIVE:To identify mutation-specific cancer risks for carriers of BRCA1/2. DESIGN, SETTING, AND PARTICIPANTS:Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. EXPOSURES:Mutations of BRCA1 or BRCA2. MAIN OUTCOMES AND MEASURES: Breast and ovarian cancer risks. RESULTS:Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. CONCLUSIONS AND RELEVANCE: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.
    JAMA The Journal of the American Medical Association 04/2015; 313(13):1347-61. DOI:10.1001/jama.2014.5985 · 30.39 Impact Factor
  • M. Siu · J. Ho · I. Chuek · J. Chen · A. Kwong · V. Shin
    The Breast 03/2015; 24:S42-S43. DOI:10.1016/S0960-9776(15)70097-4 · 2.58 Impact Factor
  • A. Kwong · J. Chen · V. Shin · F. Law · T. Chan · J. Ford
    The Breast 03/2015; 24:S73. DOI:10.1016/S0960-9776(15)70182-7 · 2.58 Impact Factor
  • Michael Co · Ava Kwong
    [Show abstract] [Hide abstract]
    ABSTRACT: In patients with negative sentinel lymph node biopsy (SLNB), axillary dissection (AD) can be avoided to reduce morbidities. However, there is only limited data on the rate of positive non-SLN (NSLN) in those who have micrometastasis and isolated tumor cells (ITC) in the literature. We did a retrospective review of all clinically node-negative breast cancer patients with SLNB done at our unit from January 2001 to June 2011. Multivariate analysis was adopted to evaluate the risk factors for NSLN metastasis. Difference in 5-year disease-free survival (DFS) was evaluated with log-rank test. Five-hundred and thirty-seven patients underwent SLNB; 161 (30 %) had positive SLN on frozen section (FS), 50 of these patients (31 %) had NSLN metastasis, 25 patients had negative SLN on FS but were found to have micrometastasis on histopathology, and only 1 (4 %) of them had NSLN metastasis, while 14 patients were found to have ITC in SLN; none of them had NSLN metastasis. Multivariate analysis found that the number of SLN harboring micrometastasis is the only independent risk factor for NSLN metastasis in patients with micrometastasis (p value = 0.008). On the contrary; tumor size, grade, and biology were not associated with NSLN metastasis. 5-year DFS in patients with macrometastasis in SLN was 94.2 %, while that in patients with micrometastasis and ITC was 100 % (p value <0.001). NSLN metastasis in those who only have micrometastasis and ITC is rare, and 5-year DFS is significantly better in this group of patients as well. It is therefore a routine practice in our unit to omit AD in patients with micrometastasis and ITC on SLN.
    World Journal of Surgery 02/2015; 39(6). DOI:10.1007/s00268-015-2984-x · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (miRs) have been shown to play important roles in tumour progression. Their expression pattern can be useful for cancer classification. However, little about miRs is known in mammary phyllodes tumors (PT). In this study, a PCR based miR profiling was performed in a small PT cohort to identify deregulated miRs in malignant PT. The purported roles and targets of these miRs were further validated. Unsupervised clustering of miR expression profiling segregated PT into different grades, implicating miR profile in PT classification. Among the deregulated miRs, miR-21, miR-335 and miR-155 were validated to be higher in malignant than lower grades PT in the independent cohort by qPCR (p≤0.032). Their expression correlated with some of the malignant histologic features, including high stromal cellularity, nuclear pleomorphism and mitosis. Subsequent analysis of their downstream proteins, viz. PTEN for miR-21/ miR-155 and Rb for miR-335 also showed independent significant negative association between miR and protein expression. Differential expression of miRs in PT could be useful in diagnosis and grading of PT. Their deregulated expression together with the altered downstream targets implicated their active involvement in PT malignant transformation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 01/2015; DOI:10.1111/his.12648 · 3.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: AluScan combines inter-Alu PCR using multiple Alu-based primers with opposite orientations and next-generation sequencing to capture a huge number of Alu-proximal genomic sequences for investigation. Its requirement of only sub-microgram quantities of DNA facilitates the examination of large numbers of samples. However, the special features of AluScan data rendered difficult the calling of copy number variation (CNV) directly using the calling algorithms designed for whole genome sequencing (WGS) or exome sequencing. In this study, an AluScanCNV package has been assembled for efficient CNV calling from AluScan sequencing data employing a Geary-Hinkley transformation (GHT) of read-depth ratios between either paired test-control samples, or between test samples and a reference template constructed from reference samples, to call the localized CNVs, followed by use of a GISTIC-like algorithm to identify recurrent CNVs and circular binary segmentation (CBS) to reveal large extended CNVs. To evaluate the utility of CNVs called from AluScan data, the AluScans from 23 non-cancer and 38 cancer genomes were analyzed in this study. The glioma samples analyzed yielded the familiar extended copy-number losses on chromosomes 1p and 9. Also, the recurrent somatic CNVs identified from liver cancer samples were similar to those reported for liver cancer WGS with respect to a striking enrichment of copy-number gains in chromosomes 1q and 8q. When localized or recurrent CNV-features capable of distinguishing between liver and non-liver cancer samples were selected by correlation-based machine learning, a highly accurate separation of the liver and non-liver cancer classes was attained. The results obtained from non-cancer and cancerous tissues indicated that the AluScanCNV package can be employed to call localized, recurrent and extended CNVs from AluScan sequences. Moreover, both the localized and recurrent CNVs identified by this method could be subjected to machine-learning selection to yield distinguishing CNV-features that were capable of separating between liver cancers and other types of cancers. Since the method is applicable to any human DNA sample with or without the availability of a paired control, it can also be employed to analyze the constitutional CNVs of individuals.
    12/2014; 4(1):15. DOI:10.1186/s13336-014-0015-z
  • W Wt Lam · R Fielding · P Butow · B J Cowling · M Chan · A Or · A Kwong · D Suen
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose:To analyse the effect of germline mutations in BRCA1 and BRCA2 on mortality in ovarian cancer patients up to ten years after diagnosis. Experimental Design:We used unpublished survival time data for 2,242 patients from two case-control studies and extended survival-time data for 4,314 patients from previously reported studies. All participants had been screened for deleterious germline mutations in BRCA1 and BRCA2. Survival time was analysed for the combined data using Cox proportional hazard models with BRCA1 and BRCA2 as time-varying covariates. Competing risks were analysed using Fine and Gray model. Results: The combined 10-year overall survival was 30% (95% CI, 28%-31%) for non-carriers, 25% (95% CI, 22%-28%) for BRCA1 carriers, and 35% (95% CI, 30%-41%) for BRCA2 carriers. The hazard ratio for BRCA1 was 0.53 at time zero and increased over time becoming greater than one at 4.8 years. For BRCA2, the hazard ratio was 0.42 at time zero and increased over time (predicted to become greater than one at 10.5 years). The results were similar when restricted to 3,202 patients with high-grade serous tumors, and to ovarian cancer specific mortality. Conclusions: BRCA1/2 mutations are associated with better short-term survival, but this advantage decreases over time and, in BRCA1 carriers is eventually reversed. This may have important implications for therapy of both primary and relapsed disease and for analysis of long-term survival in clinical trials of new agents, particularly those that are effective in BRCA1/2 mutation carriers.
    Clinical Cancer Research 11/2014; 21(3). DOI:10.1158/1078-0432.CCR-14-2497 · 8.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Around 80% of mutations in the PTEN gene have been reported to be associated with diseases such as Cowden syndrome, which is an autosomal dominant disorder associated with an increased risk of developing breast, thyroid, and endometrial neoplasms. Recent studies have also demonstrated that KILLIN, which is located proximally to PTEN, shares the same transcription start site, and is assumed to be regulated by the same promoter, but is transcribed in the opposite direction. In this regard, we postulate that there may be a connection between KILLIN/PTEN genes and breast and thyroid cancers. Using real-time quantitative polymerase chain reaction (qPCR), we found that expression of KILLIN, but not PTEN, was significantly decreased in 23 Chinese women with a personal history of breast and thyroid cancer or a personal history of breast cancer and a family history of thyroid cancer, or vice versa, and at least two persons in the family with thyroid cancer or at a young age <40 years, when compared with healthy controls (P<0.0001). No PTEN mutations were found in these 23 patients. We then developed a simple methylation-sensitive restriction enzyme digestion followed by real-time quantitative assay to quantify plasma methylated KILLIN/PTEN DNA in these patients. Plasma levels of methylated KILLIN/PTEN DNA were significantly increased in these patients when compared with healthy controls (P<0.05). This study shows that plasma methylated KILLIN/PTEN DNA was significantly elevated, suggesting hypermethylation of the KILLIN/PTEN promoter in breast and thyroid cancer patients.
    OncoTargets and Therapy 11/2014; 7:2085-2092. DOI:10.2147/OTT.S53597 · 2.31 Impact Factor
  • Vivian Y. Shin · Man T. Siu · John C. Ho · Ava Kwong
    Cancer Research 10/2014; 74(19 Supplement):531-531. DOI:10.1158/1538-7445.AM2014-531 · 9.28 Impact Factor
  • M Rushton · A Kwong · H Visram · N Graham · W Petrcich · S Dent
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Male breast cancer (BC) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female BC. The objective of the present study was to compare disease-free (DFS) and overall survival (os) for men compared with women having early-stage BC. Methods This retrospective case-control study compared men and women treated for stage 0-IIIB BC at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan-Meier analysis was used to calculate os and DFS. Results For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean DFS was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both DFS and os was stage at diagnosis. Conclusions This case-control study is one of the largest to report treatment outcomes in early-stage male BC patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and DFS. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.
    Cancer Research 06/2014; 21(3):e400-7. DOI:10.3747/co.21.1730 · 9.28 Impact Factor
  • A. Kwong · CH Au · FB Law · DN Ho · BK Ip · AT Wong · VY Shin · TL Chan · ES Ma
    Cancer Research 03/2014; 73(24 Supplement):P2-07-03-P2-07-03. DOI:10.1158/0008-5472.SABCS13-P2-07-03 · 9.28 Impact Factor

Publication Stats

683 Citations
507.98 Total Impact Points

Institutions

  • 2008–2015
    • Hong Kong Sanatorium & Hospital
      Hong Kong, Hong Kong
    • The University of Hong Kong
      • Department of Surgery
      Hong Kong, Hong Kong
  • 2014
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 2007–2014
    • Queen Mary Hospital
      Hong Kong, Hong Kong
  • 2007–2013
    • Stanford University
      • • Department of Surgery
      • • Department of Radiology
      Palo Alto, California, United States
  • 2012
    • University of Cambridge
      • Department of Public Health and Primary Care
      Cambridge, England, United Kingdom
  • 2011
    • Hong Kong Hospital Authority
      Hong Kong, Hong Kong
  • 2007–2008
    • Stanford Medicine
      • Department of Surgery
      Stanford, California, United States