Ava Kwong

The University of Hong Kong, Hong Kong, Hong Kong

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Publications (99)482.65 Total impact

  • 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
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    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; DOI:10.1038/bjc.2015.143 · 4.82 Impact Factor
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    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
  • The Breast 03/2015; 24:S42-S43. DOI:10.1016/S0960-9776(15)70097-4 · 2.58 Impact Factor
  • The Breast 03/2015; 24:S73. DOI:10.1016/S0960-9776(15)70182-7 · 2.58 Impact Factor
  • Michael Co, Ava Kwong
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    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
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    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
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    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.
  • Cancer Research 10/2014; 74(19 Supplement):531-531. DOI:10.1158/1538-7445.AM2014-531 · 9.28 Impact Factor
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    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
  • 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
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    ABSTRACT: Western studies have shown that the uptake rates of surveillance and prophylaxis may vary among BRCA mutation carriers between ethnicities. The present study is the first to investigate the behavioural impact and subjective attitudes in Southern Chinese high-risk families who had undergone BRCA1 and BRCA2 genetic testing up to 2.5 years post-testing. Individuals who had such genetic testing and have consented to participate in the prospective database of Hong Kong Hereditary Breast Cancer Family Registry were recruited and surveyed by a face-to-face or telephone interview. Sociodemographic information, genetic test results, pre- and post-testing surveillance, medical regimes, and attitudes towards the choice of clinical management were obtained by interviews and retrieval of medical records using this prospective database. 69 females with breast cancer history were recruited into the study. Twenty-nine female carriers (15 BRCA1 mutated gene-carriers and 14 BRCA2 mutated gene-carriers) and 40 non-carriers of a BRCA 1/2 mutations were interviewed. The uptake rate of high risk breast screening i.e. clinical breast examination, mammography, and breast MRI is significantly higher among female carriers (48.3 %) after knowing genetic testing results than before (p < 0.01). A strong significant relationship between any increase or decrease of ovarian ultrasound screening (OS) and genetic status is found (p < .001), with more females did OS and with a higher frequency after knowing genetic testing results among both carriers (22.7 % → 86.4 %) and non-carriers (37.5 % → 50.0 %). Among carriers, very few opted for prophylactic surgeries. The present cohort might see prophylaxis as last resort and would use traditional Chinese medicine in cancer risk management.
    Familial Cancer 03/2014; DOI:10.1007/s10689-014-9706-7 · 1.62 Impact Factor
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    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 01/2014; 7:2085-2092. DOI:10.2147/OTT.S53597 · 1.34 Impact Factor
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    ABSTRACT: Stress adaptation has profound consequences for malignant progression and the response to therapy. BRCA1 is an important modulator of cellular stress, but our understanding of its mechanisms of action remains incomplete. Here we identify autophagy as an essential mechanism protecting BRCA1 deficient cancer cells from metabolic stress and allow their survival, which may underlie its significant cancer-promoting properties. We showed that targeted inhibition of endogenous BRCA1 using small interfering RNA caused significant autophagy in response to serum starvation and endoplasmic reticulum stress, whereas overexpression of BRCA1 did not, confirming that the effect was BRCA1 specific. We demonstrated that Beclin 1 was activated in BRCA1 deficient cells, suggesting involvement of a canonical pathway. Importantly, BRCA1 deficient cells were highly dependent on autophagy for survival, and rapidly underwent cell death upon disruption of autophagy. Notably, this dependence on protective autophagy extended to their tissue of origin, as ovarian surface epithelial cells from women testing positive for BRCA1 mutations, in contrast to those with no mutations, robustly induced autophagy to mitigate the stress and promote their survival. These findings highlight a novel role for BRCA1 in protective autophagy, which may make its essential contribution to tumorigenesis and prognosis.
    Cancer letters 12/2013; 346(1). DOI:10.1016/j.canlet.2013.12.026 · 5.02 Impact Factor
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    ABSTRACT: Male breast cancer (MBC) is uncommon. As a result, there is limited availability of studies and reviews and even fewer reports from Asia. This is the largest population-based study to compare Chinese MBC patients with female patients during a 10-year period in Hong Kong, Southern China. A retrospective review of medical records of 132 male and 8,118 female breast cancer patients between year 1997 and 2006 in Hong Kong was performed. Each MBC patient was matched with three female breast cancer patients for further analysis. Different characteristics, overall, breast-cancer specific, and disease-free survivals (DFS) were compared. Mean age at diagnosis of male and female patients was 64.5 and 52.7 years respectively. Male patients showed lower histological grade, overall stage, smaller tumor size, and more positive sensitivity in hormone receptors. They were more likely to die of causes other than breast cancer. Matched analysis found that the 5-year overall survival (OS), breast-cancer-specific mortality, and DFS for male and female patients were 78.7, 90.5, 90.5, and 77.9, 86.4, and 81.4 % respectively. Male patients had poorer OS at early overall stage but better breast-cancer-specific mortality rates at any age (p < 0.01). Male patients had a significant risk of dying due to any cause in the presence of distant relapse and had less risk of dying when tumor was ER-positive and HER2-positive. Chinese male breast cancer patients tend to have poorer OS but better breast-cancer-specific survival compared with their female counterparts.
    Annals of Surgical Oncology 12/2013; DOI:10.1245/s10434-013-3377-8 · 3.94 Impact Factor
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    ABSTRACT: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms. Copyright © 2013 John Wiley & Sons, Ltd.
    Psycho-Oncology 12/2013; 22(12). DOI:10.1002/pon.3361 · 4.04 Impact Factor
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    ABSTRACT: To assess the extent to which breast surgical consultations used shared decision making (SDM), identify factors associated with use of SDM, and assess if using SDM increases decision-making satisfaction. Two hundred and eighty-three video-recorded diagnostic-treatment decision consultations between breast surgeons and women with breast cancer were assessed using the Decision Analysis System for Oncology (DAS-O) coding system designed for assessing SDM behaviors. Women completed a questionnaire at pre-consultation, one-week post-consultation and one-month post-surgery. Patient outcomes included decision conflict, patient satisfaction with medical consultation, and decision regret. Overall, the level of SDM behaviors was low. The extent of SDM behavior within consultation was related to greater consultation duration (p<0.001), more than one treatment being offered (p<0.001), and fewer questions raised by patients/companions (p<0.05). While use of SDM consultation did not influence post-consultation decision conflict, it increased satisfaction with information given and explained, patients' feelings of trust and confidence in their surgeons, and reduced post-surgical decision regret. These breast surgical consultations mostly adopted informed treatment decision-making approaches. Using SDM improved patient consultation and decision satisfaction. The study findings highlight a need to reinforce the importance of SDM in consultations among breast surgeons.
    Patient Education and Counseling 11/2013; DOI:10.1016/j.pec.2013.11.006 · 2.60 Impact Factor

Publication Stats

615 Citations
482.65 Total Impact Points

Institutions

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