Comparison of clinical characteristics between ACOSOG Z0011-eligible cohort and sentinel lymph node-positive breast cancer patients in Hong Kong.

INTRODUCTION: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial resulted in de-escalation of axillary surgery among early-stage breast cancer patients with low-volume sentinel lymph node (SLN) disease undergoing breast-conserving surgery and radiation therapy. Nevertheless, the mastectomy rate in the Chinese population remains high. This study compared the clinical characteristics of the ACOSOG Z0011-eligible cohort with SLN-positive breast cancer patients in Hong Kong. METHODS: This retrospective analysis of a prospectively maintained database at a university-affiliated breast cancer centre in Hong Kong was performed from June 2014 to May 2019. The database included all patients with clinical tumour (T) stage T1 or T2 invasive breast carcinoma, no palpable adenopathy, one or two positive SLNs on histological examination, and no prior neoadjuvant systemic treatment. Comparisons were made between the mastectomy and breast-conserving treatment groups in our cohort, along with the sentinel-alone arm in the ACOSOG Z0011 trial. RESULTS: One hundred and seventy-one patients met the inclusion criteria: 112 underwent mastectomy and 59 underwent breast-conserving treatment. Our mastectomy group had higher prevalences of T2 tumours (P<0.001), lymphovascular invasion (P<0.001), and SLN macrometastases (P=0.004) compared with the ACOSOG Z0011 cohort. However, in our patient population, mean pathological size slightly differed between the mastectomy and breast-conserving treatment groups (2.2 cm vs 1.8 cm; P=0.005). Other histopathological features were similar. CONCLUSION: This study demonstrated that clinicopathological features were comparable between SLN-positive breast cancer patients undergoing mastectomy and those undergoing breast-conserving treatment. Low-risk SLN-positive mastectomy patients may safely avoid completion axillary lymph node dissection.

OPTN/SRTR 2020 Annual Data Report: Liver.

This year was marked by the COVID-19 pandemic, which altered transplant program activity and affected waitlist and transplant outcomes. Still, 8906 liver transplants were performed, an all-time high, across 142 centers in the United States, and pretransplant as well as graft and patient survival metrics, continued to improve. Living donation activity decreased after several years of growth. As of June 30, 2020, 98989 liver transplant recipients were alive with a functioning graft, and in the context of increasing liver transplant volume, the size of both the adult and pediatric liver transplant waitlists have decreased. On February 4, 2020, shortly before the pandemic began, a new liver distribution policy based on acuity circles was implemented, replacing donor service area- and region-based boundaries. A policy change to direct pediatric livers to pediatric recipients led to an increase in deceased donor transplant rates and a decrease in pretransplant mortality rate among children, although the absolute number of pediatric transplants did not increase in 2020. Among adults, alcohol-associated liver disease became the predominant indication for liver transplant in 2020. After implementation of the National Liver Review Board and lower waitlist priority for most exception cases in 2019, fewer liver transplants were being performed via exception points, and the transplant rate between those with and without hepatocellular carcinoma has equalized. Women continue to experience higher pretransplant mortality and lower rates of liver transplant than men.

OPTN/SRTR 2019 Annual Data Report: Liver.

This year was notable for changes to exception points determined by the geographic median allocation Model for End-Stage Liver Disease (MELD) and implementation of the National Liver Review Board, which took place on May 14, 2019. The national acuity circle liver distribution policy was also implemented but reverted to donor service area- and region-based boundaries after 1 week. In 2019, growth continued in the number of new waiting list registrations (12,767) and transplants performed (8,896), including living-donor transplants (524). Compared with 2018, living-donor liver transplants increased 31%. Women continued to have a lower deceased-donor transplant rate and a higher pretransplant mortality rate than men. The median waiting time for candidates with a MELD of 15-34 decreased, while the number of transplants performed for patients with exception points decreased. These changes may have been related to the policy changes that took effect in May 2019, which increased waiting list priority for candidates without exception status. Hepatitis C continued to decline as an indication for liver transplant, as the proportion of liver transplant recipients with alcohol-related liver disease and clinical profiles consistent with non-alcoholic steatohepatitis increased. Graft and patient survival have improved despite changing recipient demographics including older age, higher MELD, and higher prevalence of obesity and diabetes.

OPTN/SRTR 2018 Annual Data Report: Liver.

Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.

Clinical outcomes of patients with ductal carcinoma in situ in Hong Kong: 10-year territory-wide cancer registry study.

BACKGROUND: Incidence of ductal carcinoma in situ (DCIS) has increased in recent decades because of breast cancer screening. This study comprised a long-term survival analysis of DCIS using 10-year territory-wide data from the Hong Kong Cancer Registry. METHODS: This study included all patients diagnosed with DCIS in Hong Kong from 1997 to 2006. Exclusion criteria were age <30 years or ≥70 years, lobular carcinoma in situ, Paget's disease, and co-existing invasive carcinoma. Patients were stratified into those diagnosed from 1997 to 2001 and those diagnosed from 2002 to 2006. The 5- and 10-year breast cancer-specific survival rates were evaluated; standardised mortality ratios were calculated. RESULTS: Among the 1391 patients in this study, 449 were diagnosed from 1997 to 2001, and 942 were diagnosed from 2002 to 2006. The mean age at diagnosis was 49.2±9.2 years. Overall, 51.2% of patients underwent mastectomy and 29.5% received adjuvant radiotherapy. The median follow-up interval was 11.6 years; overall breast cancer-specific mortality rates were 0.3% and 0.9% after 5 and 10 years of follow-up, respectively. In total, 109 patients (7.8%) developed invasive breast cancer after a considerable delay. Invasive breast cancer rates were comparable between patients diagnosed from 1997 to 2001 (n=37, 8.2%) and those diagnosed from 2002 to 2006 (n=72, 7.6%). CONCLUSION: Despite excellent long-term survival among patients with DCIS, these patients were more likely to die of breast cancer, compared with the general population of women in Hong Kong.

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.

Implications of nipple discharge in Hong Kong Chinese women.

INTRODUCTION: There are no recent data on nipple discharge and its association with malignancy in Hong Kong Chinese women. This study reported our 5-year experience in the management of patients with nipple discharge, and our experience of mammography, ultrasonography, ductography, and nipple discharge cytology in an attempt to determine their role in the management of nipple discharge. METHODS: Women who attended our Breast Clinic in a university-affiliated hospital in Hong Kong were identified by retrospective review of clinical data from January 2007 to December 2011. They were divided into benign and malignant subgroups. Background clinical variables and investigative results were compared between the two subgroups. We also reported the sensitivity, specificity, and positive and negative predictive values of the investigations that included mammography, ultrasonography, ductography, and cytology. RESULTS: We identified 71 and 31 patients in the benign and malignant subgroups, respectively. The median age at presentation for the benign subgroup was younger than that of the malignant subgroup (48 vs 59 years; P=0.003). A higher proportion of patients in the malignant subgroup than the benign subgroup presented with blood-stained nipple discharge (87.1% vs 47.9%; P=0.002). Mammography had a specificity of 98.4% and positive predictive value of 66.7%; ultrasonography had a specificity of 87.0% and negative predictive value of 75.0%. Cytology and ductography were sensitive but lacked specificity. Ductography had a negative predictive value of 100% but a low positive predictive value (14.0%). Clinical variables including age at presentation, duration of discharge, colour of discharge, presence of an associated breast mass, and abnormal sonographic findings were important in suggesting the underlying pathology of nipple discharge. Multiple logistic regression showed that blood-stained discharge and an associated breast mass were statistically significantly more common in the malignant subgroup. CONCLUSIONS: In patients with non-blood-stained nipple discharge, a negative clinical breast examination combined with negative imaging could reasonably infer a benign underlying pathology.

Clinical and biochemical characteristics of infants with prolonged neonatal jaundice.

INTRODUCTION: Protocols for investigating neonatal prolonged jaundice vary and the yield from screening has not been assessed. International guidelines recommend establishing cholestasis before proceeding to investigate the underlying pathology. However, in most hospitals administered by the Hospital Authority, full liver function is checked at the first neonatal jaundice clinic visit. To study the diagnostic yield of this approach, we carried out a retrospective study of all infants referred for prolonged jaundice. METHODS: Attendance records from the neonatal jaundice clinic at the Tuen Mun Hospital, Hong Kong, the clinical management system, and electronic patient records were used to retrieve epidemiological, clinical, and laboratory data, and patients' clinical progress. RESULTS: During the 8-month study period from 8 July 2015 to 8 March 2016, 1164 infants were referred to the neonatal jaundice clinic for prolonged jaundice. Among them, 16 (1.4%) infants had conjugated hyperbilirubinaemia. Diagnoses included biliary atresia (n=1), cytomegalovirus (CMV) infection (n=3), neonatal hepatitis syndrome (n=2), and transient cholestasis (n=10). In total, 98 (8.42%) infants had elevated alanine transaminase levels. Diagnoses included biliary atresia (n=1), hepatic congestion related to congestive heart failure (n=1), CMV infection (n=5), neonatal hepatitis syndrome (n=16), and non-specific elevated alanine transaminase (n=75). In total, 59 infants had elevated alkaline phosphatase levels. CONCLUSIONS: A stepwise approach is recommended, in which full liver function is checked and the underlying cause of jaundice is investigated only after confirming cholestasis.

Comparing the meanings of living with advanced breast cancer between women resilient to distress and women with persistent distress: a qualitative study.

BACKGROUND: Most women with advanced breast cancer (ABC) show little distress, but about one in ten show persistent distress over time. It remains unclear if meanings ascribed by patients to ABC differentiate these distress trajectories. STUDY AIMS: This qualitative study (a) compared illness meanings of ABC between women with persistent psychological distress and those with low/transient distress, and (b) examined how illness meanings might influence coping strategies. METHODS: The sample was drawn from a prior quantitative study exploring psychological distress trajectories following ABC diagnosis. Overall, 42 Cantonese- or Mandarin-speaking Chinese women diagnosed with locally advanced or metastatic ABC were recruited based on their distress trajectory status (low-stable, transient, or persistent distress). Interviews were recorded, transcribed, and analyzed following grounded theory approach using simultaneous analysis. RESULTS: Women with persistent distress viewed their diagnosis as another blow in life, the illness was global, permeating every aspect of their life. Maladaptive rumination and thought suppression were common responses to illness demands. These women had poor social support. A sense of demoralization stood out in their narratives. In contrast, women with transient/low-stable distress encapsulated the illness, with minimum impacts of their life. They did not evidence dysfunctional repetitive thoughts. Living in a supportive environment, they were able to accept and/or live in the present-moment. CONCLUSIONS: Rumination, thought suppression, social constraints, and pre-existing exposure to life stress may be potential risks for chronic distress in response to advanced breast cancer. Persistent and transient distress responses to cancer may have different underpinnings. Copyright © 2016 John Wiley & Sons, Ltd.

A prospective randomised controlled trial of octylcyanoacrylate tissue adhesive and standard suture for wound closure following breast surgery.

INTRODUCTION: Several studies have demonstrated that octylcyanoacrylate tissue adhesive provides an equivalent cosmetic outcome as standard suture for wound closure. This study aimed to compare octylcyanoacrylate tissue adhesive with standard suture for wound closure following breast surgery. METHODS: A prospective randomised controlled trial was conducted in a public hospital in Hong Kong. A total of 70 female patients, who underwent elective excision of clinically benign breast lump between February 2009 and November 2011, were randomised to have wound closure using either octylcyanoacrylate tissue adhesive or standard wound suture following breast surgery. Wound complications and cosmetic outcome were measured. RESULTS: Octylcyanoacrylate tissue adhesive achieved wound closure in significantly less time than standard suturing (mean, 80.6 seconds vs 344.6 seconds; P<0.001). There was no statistical difference in wound condition or cosmetic outcome although number of clinic visits, ease of self-showering, and comfort of dressing significantly favoured octylcyanoacrylate tissue adhesive. CONCLUSIONS: Octylcyanoacrylate tissue adhesive may be offered as an option for wound closure following breast surgery.

Circulating cell-free miRNAs as biomarker for triple-negative breast cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Treatment outcomes for male breast cancer: a single-centre retrospective case-control study.

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.

Automated identification of abnormal infant movements from smart phone videos.

Cerebral palsy (CP) is the most common cause of physical disability during childhood, occurring at a rate of 2.1 per 1000 live births. Early diagnosis is key to improving functional outcomes for children with CP. The General Movements (GMs) Assessment has high predictive validity for the detection of CP and is routinely used in high-risk infants but only 50% of infants with CP have overt risk factors when they are born. The implementation of CP screening programs represents an important endeavour, but feasibility is limited by access to trained GMs assessors. To facilitate progress towards this goal, we report a deep-learning framework for automating the GMs Assessment. We acquired 503 videos captured by parents and caregivers at home of infants aged between 12- and 18-weeks term-corrected age using a dedicated smartphone app. Using a deep learning algorithm, we automatically labelled and tracked 18 key body points in each video. We designed a custom pipeline to adjust for camera movement and infant size and trained a second machine learning algorithm to predict GMs classification from body point movement. Our automated body point labelling approach achieved human-level accuracy (mean ± SD error of 3.7 ± 5.2% of infant length) compared to gold-standard human annotation. Using body point tracking data, our prediction model achieved a cross-validated area under the curve (mean ± S.D.) of 0.80 ± 0.08 in unseen test data for predicting expert GMs classification with a sensitivity of 76% ± 15% for abnormal GMs and a negative predictive value of 94% ± 3%. This work highlights the potential for automated GMs screening programs to detect abnormal movements in infants as early as three months term-corrected age using digital technologies.

Antidepressant Exposure and DNA Methylation: Insights from a Methylome-Wide Association Study.

Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-2011 in Generation Scotland (GS). The summary statistics were tested for enrichment in specific tissues, gene ontologies and an independent MWAS in the Netherlands Study of Depression and Anxiety (NESDA). A methylation profile score (MPS) was derived and tested for its association with antidepressant exposure in eight independent cohorts, alongside prospective data from GS. Setting: Cohorts; GS, NESDA, FTC, SHIP-Trend, FOR2107, LBC1936, MARS-UniDep, ALSPAC, E-Risk, and NTR. Participants: Participants with DNAm data and self-report/prescription derived antidepressant exposure. Main Outcomes and Measures: Whole-blood DNAm levels were assayed by the EPIC/450K Illumina array (9 studies, N exposed = 661, N unexposed = 9,575) alongside MBD-Seq in NESDA (N exposed = 398, N unexposed = 414). Antidepressant exposure was measured by self- report and/or antidepressant prescriptions. Results: The self-report MWAS (N = 16,536, N exposed = 1,508, mean age = 48, 59% female) and the prescription-derived MWAS (N = 7,951, N exposed = 861, mean age = 47, 59% female), found hypermethylation at seven and four DNAm sites (p < 9.42x10 -8 ), respectively. The top locus was cg26277237 ( KANK1, p self-report = 9.3x10 -13 , p prescription = 6.1x10 -3 ). The self-report MWAS found a differentially methylated region, mapping to DGUOK-AS1 ( p adj = 5.0x10 -3 ) alongside significant enrichment for genes expressed in the amygdala, the "synaptic vesicle membrane" gene ontology and the top 1% of CpGs from the NESDA MWAS (OR = 1.39, p < 0.042). The MPS was associated with antidepressant exposure in meta-analysed data from external cohorts (N studies = 9, N = 10,236, N exposed = 661, f3 = 0.196, p < 1x10 -4 ). Conclusions and Relevance: Antidepressant exposure is associated with changes in DNAm across different cohorts. Further investigation into these changes could inform on new targets for antidepressant treatments. 3 Key Points: Question: Is antidepressant exposure associated with differential whole blood DNA methylation?Findings: In this methylome-wide association study of 16,536 adults across Scotland, antidepressant exposure was significantly associated with hypermethylation at CpGs mapping to KANK1 and DGUOK-AS1. A methylation profile score trained on this sample was significantly associated with antidepressant exposure (pooled f3 [95%CI]=0.196 [0.105, 0.288], p < 1x10 -4 ) in a meta-analysis of external datasets. Meaning: Antidepressant exposure is associated with hypermethylation at KANK1 and DGUOK-AS1 , which have roles in mitochondrial metabolism and neurite outgrowth. If replicated in future studies, targeting these genes could inform the design of more effective and better tolerated treatments for depression.

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The relationship between timing of onset of menarche and depressive symptoms from adolescence to adulthood.

AIMS: Girls who experience an earlier onset of menarche than their peers are at increased risk of depressive symptoms in mid-adolescence, but it is unclear if this association persists into adulthood. This study examines whether longitudinal patterns of depressive symptoms from adolescence to adulthood vary according to timing of menarche. METHODS: About 4,864 female participants in the UK Avon Longitudinal Study of Parents and Children provided data on age at onset of menarche (assessed in repeated questionnaires from 8 to 17 years) and depressive symptoms across nine time points (13 to 26 years) using the Short Mood and Feelings Questionnaire. We compared patterns of depressive symptoms in girls with 'early' (<11.5 years), 'normative' (11.5 to 13.5 years) and 'late' (≥13.5 years) menarche using a linear spline multilevel growth curve model adjusted for indicators of socioeconomic position, father absence and body mass index. RESULTS: Early, compared with normative, menarche was associated with higher levels of depressive symptoms at age 14 (imputed adjusted estimated difference = 0.94, 95% confidence interval [CI] = 0.44, 1.45), but the association attenuated at 24 years (0.24 [-0.72, 1.19]). Late menarche, compared with normative, was associated with a lower level of depressive symptoms at age 14 (-0.69 [-1.10, -0.29]), but this association also attenuated at 24 years (-0.15 [-0.92, 0.62]). CONCLUSIONS: This study did not find a persistent effect of early menarche, compared to normative, on depressive symptoms. However, our findings are consistent with the level of depressive symptoms increasing at the onset of menarche irrespective of timing. The late onset girls 'catch up' with their peers who experience menarche earlier in terms of depressive symptoms. Future studies should continue to assess the impact of timing of menarche further into adulthood.

Resveratrol enhanced chemosensitivity by reversing macrophage polarization in breast cancer.

BACKGROUND: Resveratrol, a naturally occurring polyphenolic compound, has been shown to inhibit cancer growth by targeting several cancer-related signalling pathways. In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant leukocyte population that are associated with poor prognosis in over 80% of breast cancer cases. However, little is known about the effect of resveratrol in the TME. METHODS: In this study, MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR), and T47D were used to examine the antitumor effect of resveratrol. The effectiveness of resveratrol, together with cisplatin as breast cancer treatment was investigated in vivo. Gene expressions of M1 (iNOS and CXCL10) and M2 (ARG1, CD163 and MRC1) markers in differentiated macrophages derived from THP-1 cells were examined to investigate the effect of resveratrol on TAM polarization in breast cancer progression. RESULTS: Our results demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in breast cancer cells by inhibiting production of IL-6 and STAT3 activation. Treatment of resveratrol increased CXCL10 (M1 marker) expression. Further, resveratrol decreased IL-6 levels in LPS-treated differentiated macrophages. The use of resveratrol with cisplatin inhibited suppressed tumor growth when compared with cisplatin alone. CONCLUSION: This study revealed that resveratrol inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and suppressing IL-6/pSTAT3 pathway.