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Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong

Objective: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy. Design: Retrospective study. Setting: Clinical oncology department in a public hospital in Hong Kong. Patients: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006. Results: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. Conclusion: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.published_or_final_versio

HER2 overexpression of breast cancers in Hong Kong: Prevalence and concordance between immunohistochemistry and in-situ hybridisation assays

Objectives: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. Design: Retrospective study. Setting: Department of Clinical Oncology in a public hospital in Hong Kong. Patients: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). Results: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. Conclusions: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.published_or_final_versio

IgG antibody responses to Plasmodium falciparum merozoite antigens in Kenyan children have a short half-life

BACKGROUND: Data suggest that antibody responses to malaria parasites merozoite antigens are generally short-lived and this has implications for serological studies and malaria vaccine designs. However, precise data on the kinetics of these responses is lacking. METHODS: IgG1 and IgG3 responses to five recombinant Plasmodium falciparum merozoite antigens (MSP-119, MSP-2 type A and B, AMA-1 ectodomain and EBA-175 region II) among Kenyan children were monitored using ELISA for 12 weeks after an acute episode of malaria and their half-lives estimated using an exponential decay model. RESULTS: The responses peaked mainly at week 1 and then decayed rapidly to very low levels within 6 weeks. Estimation of the half-lives of 40 IgG1 responses yielded a mean half-life of 9.8 days (95% CI: 7.6-12.0) while for 16 IgG3 responses it was 6.1 days (95% CI: 3.7-8.4), periods that are shorter than those normally described for the catabolic half-life of these antibody subclasses. CONCLUSION: This study indicates antibodies against merozoite antigens have very short half-lives and this has to be taken into account when designing serological studies and vaccines based on the antigens

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic nonsteroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4- aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter antiinflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs

Trends and Patterns of Breast Conservation Treatment in Hong Kong: 1994-2007

Purpose: Breast conservation treatment (BCT) was quite unpopular in Hong Kong until the early 1990s, but the trends and patterns of BCT use in the past 14 years have not been studied since. The purpose of this study was to identify the latest trends and patterns. Methods and Materials: All consecutive cases of female breast cancer referred to a community oncology center in Hong Kong between 1994 and 2007 were retrospectively reviewed. Of the 2,375 women with T1-2 invasive breast cancer who underwent surgery, 1,137 (48%) had T1 (≤2 cm) disease and 1,238 (52%) had T2 (>2 cm-≤5 cm) disease. Median patient age was 51 years (range, 24-95 years); 65% patients had their surgery in public hospitals. Results: Of the total patient cohort, 2,153 (91%) patients presented with palpable breast masses and only 104 (4%) with mammographically detected cancers. Overall, 721 (30%) and 1,654 (70%) patients underwent BCT and mastectomy, respectively. There was no significant increase in the BCT rates (31%, SD 5%; p = 0.804) or mammographic detection rates (5%, SD 1%; p = 0.125) in Hong Kong between 1994 and 2007. In multivariate analyses, age ≤50 years (OR 2.479; p < 0.001), mammographically detected tumors (OR 1.868; p = 0.007), T1 tumors (OR 3.159; p < 0.001), surgeries in private hospitals (OR 1.288; p = 0.018), and negative nodal status (OR 1.886; p < 0.001) were independent factors predictive of a higher likelihood of a woman having BCT. Conclusions: Our results indicate a satisfactory acceptance of BCT by patients who are young and have small tumors, node-negative disease, or surgery in private hospitals. However, the continuing unpopularity of breast screening is likely a major factor limiting the broad use of BCT. © 2009 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Surveillance mammography after breast conservation therapy in Hong Kong: Effectiveness and feasibility of risk-adapted approach

Annual surveillance mammography is commonly recommended after breast conservation therapy (BCT). We retrospectively reviewed its effectiveness on 511 invasive and non-invasive breast cancers treated with BCT between 1994 and 2003. The median follow-up was 5.9 years. The 5-year actuarial ipsilateral breast tumour recurrence (IBTR) rate was 4.5% and contralateral breast cancer (CBC) rate was 2.0% (representing eight times increase in risk). IBTR of 43% and 62% CBC were first detected by surveillance mammography. The IBTR detection rates per 1000 mammograms were 5.2 for patients (n=349) with one or more IBTR risk factors (age ≤45, positive/close margins or histological grade 3) and 0.6 for patients (n=162) without. No survival difference was observed between different modes of IBTR detection (p=0.342). In conclusion, a risk-adapted approach of limiting ipsilateral surveillance to patients with IBTR risk is possible but its implementation will be complicated by the continued need of contralateral surveillance. © 2007 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex