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Abstract Background In 2008, the outbreak of kidney stones in children fed by melamine-tainted milk products in Mainland China has caused major public concern of food safety. We identified Hong Kong school children with elevated urine melamine level from a community-based school survey in 2007-08 and reviewed their clinical status in 2009. Methods In 2007-08, 2119 school children participated in a primary and secondary school survey in Hong Kong using a cluster sampling method. Urine aliquots from 502 subjects were assayed for melamine level. High urine melamine level was defined as urine melamine/creatinine ratio >7.1 μg/mmol. Subjects with high urine melamine level were invited for clinical evaluation in 2009 including urinalysis and ultrasound imaging of the urinary system. Results The age range of this subcohort was 6 - 20 years with 67% girls (335 female and 167 male subjects). The spot urine melamine/creatinine ratio of the 502 urine aliquots ranged from undetectable to 1467 μg/mmol (median 0.8 μg/mmol). Of these, 213 subjects had undetectable level (42%). We invited 47 (9%) subjects with high urine melamine level for re-evaluation and one subject declined. The median duration of follow-up was 23.5 months (interquartile range: 19.8 - 30.6 months). None of the 46 subjects (28% boys, mean age 13.9 ± 2.9 years) had any abnormality detected on ultrasound study of the urinary system. All subjects had stable renal function with a median urine albumin-creatinine ratio of 0.70 mg/mmol (interquartile range: 0.00 - 2.55 mg/mmol). Conclusions Hong Kong Chinese school children with high urine melamine levels appeared to have benign clinical course in the short term although a long term follow-up study is advisable in those with persistently high urine melamine level.

Abstract Background Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients. Methods In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD. Results The multivariate-adjusted HR (95% confidence interval) of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L) was 1.36 (1.08 - 1.71), compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol (≥ 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in patients with metabolic syndrome [(HR = 0.58(0.42--0.80)]. Conclusions In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.

Abstract Background Childhood and adolescence are critical periods of habit formation with substantial tracking of lifestyle and cardiovascular risk into adulthood. There are various guidelines on recommended levels of physical activity in youth of school-age. Despite the epidemic of obesity and diabetes in China, there is a paucity of data in this regard in Chinese youth. We examined the association of self-reported level of physical activity and cardiovascular risk in Hong Kong Chinese youth of school-age. Methods This was a cross-sectional study conducted in 2007-8 in a school setting with 2119 Hong Kong Chinese youth aged 6-20 years. Physical activity level was assessed using a validated questionnaire, CUHK-PARCY (The Chinese University of Hong Kong: Physical Activity Rating for Children and Youth). A summary risk score comprising of waist circumference, blood pressure, fasting plasma glucose and lipids was constructed to quantify cardiovascular risk. Results In this cohort, 21.5% reported high level of physical activity with boys being more active than girls (32.1% versus 14.1%, p < 0.001). Regression analysis showed physical activity level, sex and pubertal stage were independently associated with cardiovascular risk score. Conclusion Self-reported level of physical activity is associated with cardiovascular risk factors in Chinese youth after adjusting for sex and pubertal stage.

Abstract Background The risk-benefit ratio of aspirin therapy in prevention of cardiovascular disease (CVD) remains contentious, especially in type 2 diabetes. This study examined the benefit and harm of low-dose aspirin (daily dose < 300 mg) in patients with type 2 diabetes. Methods This is a longitudinal observational study with primary and secondary prevention cohorts based on history of CVD at enrolment. We compared the occurrence of primary composite (non-fatal myocardial infarction or stroke and vascular death) and secondary endpoints (upper GI bleeding and haemorrhagic stroke) between aspirin users and non-users between January 1995 and July 2005. Results Of the 6,454 patients (mean follow-up: median [IQR]: 4.7 [4.4] years), usage of aspirin was 18% (n = 1,034) in the primary prevention cohort (n = 5731) and 81% (n = 585) in the secondary prevention cohort (n = 723). After adjustment for covariates, in the primary prevention cohort, aspirin use was associated with a hazard-ratio of 2.07 (95% CI: 1.66, 2.59, p < 0.001) for primary endpoint. There was no difference in CVD event rate in the secondary prevention cohort. Overall, aspirin use was associated with a hazard-ratio of 2.2 (1.53, 3.15, p < 0.001) of GI bleeding and 1.71 (1.00, 2.95, p = 0.051) of haemorrhagic stroke. The absolute risk of aspirin-related GI bleeding was 10.7 events per 1,000 person-years of treatment. Conclusion In Chinese type 2 diabetic patients, low dose aspirin was associated with a paradoxical increase in CVD risk in primary prevention and did not confer benefits in secondary prevention. In addition, the risk of GI bleeding in aspirin users was rather high.

Abstract Background There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM. Methods 7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset. Results During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m2) + 0.1363 × HbA1c(%) + 0.9915 × Log10(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S0(5)EXP{0.9744 × (Risk Score - 2.3961)}. Where S0(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up. Conclusion The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.

Abstract Background Obesity is now a global epidemic. In this study, we aimed to assess the rates of obesity using several major diagnostic criteria in Chinese school adolescents in Hong Kong. Methods This is a cross-sectional study. Using a computer-generated coding system, we randomly selected schools from different geographical regions in Hong Kong to obtain a representative sample. Subjects aged 11–18 years of age were randomly selected from different class of the schools. Their rates of obesity according to four different international and local criteria were compared [International Obesity Task Force (IOTF) 2000 criterion; the Group of China Obesity Task Force (COTF) 2004 criterion; Centers for Disease Control and Prevention (CDC) 2000 Growth Charts and the Hong Kong Growth Survey (HKGS) charts in 1993]. Results Of the 2098 adolescents [982 (46.8%) boys and 1116 (53.2%) girls], the mean age (± SD) was 15.1 ± 1.8 years (range: 11–18 years; median: 15.0 years). The crude rates of obesity were similar based on IOTF, COTF or CDC criteria (boys: 3.9–6.0%, girls: 1.8–3.7%), however, the rate increased to 11–27% if the HKGS charts were used. Obesity rate varied markedly according to age. It decreased from 8–10% among those aged 12–13 years to 2–4% among those aged 17–18 years. Conclusion The prevalence of obesity in Hong Kong adolescents using various diagnostic criteria were similar except for the 1993 HKGS criteria, which gave an exceeding high figure. Using the IOTF, COTF or CDC criteria, the adolescent obesity in Hong Kong varied from 1.8% to 6.0%.

Abstract Background Glycated haemoglobin (HbA1c), blood pressure and body mass index (BMI) are risk factors for albuminuria, the latter in turn can lead to hyperlipidaemia. We used novel statistical analyses to examine how albuminuria and chronic kidney disease (CKD) may influence the effects of other risk factors on coronary heart disease (CHD). Methods A prospective cohort of 7067 Chinese type 2 diabetic patients without history of CHD enrolled since 1995 were censored on July 30th, 2005. Cox proportional hazard regression with restricted cubic spline was used to auto-select predictors. Hazard ratio plots were used to examine the risk of CHD. Based on these plots, non-linear risk factors were categorised and the categorised variables were refitted into various Cox models in a stepwise manner to confirm the findings. Results Age, male gender, duration of diabetes, spot urinary albumin: creatinine ratio, estimated glomerular filtration rate, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and current smoking status were risk factors of CHD. Linear association between TC and CHD was observed only in patients with albuminuria. Although in general, increased HDL-C was associated with decreased risk of CHD, full-range HDL-C was associated with CHD in an A-shaped manner with a zenith at 1.1 mmol/L. Albuminuria and CKD were the main contributors for the paradoxically positive association between HDL-C and CHD for HDL-C values less than 1.1 mmol/L. Conclusion In type 2 diabetes, albuminuria plays a linking role between conventional risk factors and CHD. The onset of CKD changes risk associations between lipids and CHD.

Competing Interests: Declaration of Competing Interest Dr. Julie Bradley – Provisional patent for breast tissue expander; no specific grant or external funding was received for this work. Editor Conflict of Interest. Given their role as Editorial Board Member, Amanda L. Kong, MD, MS, had no involvement in the peer review of this article and has no access to information regarding its peer review.

Introduction: Nipple-sparing mastectomy (NSM) with deep inferior epigastric perforator (DIEP) flap reconstruction is a surgical option for select patients with or at risk of breast cancer. However, post-operative skin flap and nipple-areolar complex (NAC) necrosis remain common complications. This study aimed to identify factors associated with necrosis in patients undergoing NSM with DIEP reconstruction., Methods: A retrospective cohort study was performed from 2015 to 2023. 74 variables were analyzed in patients undergoing NSM with DIEP. Patients were stratified into 3 groups based on post-operative skin/NAC necrosis: none, partial thickness, and full thickness. Comparative and descriptive statistics were performed via t-tests, ANOVA, and chi-squared tests., Results: 34 women with 31 breast cancers met inclusion. 44% experienced necrosis: 15% partial thickness and 29% full thickness. The majority were white (85.3%) with mean age of 50 years (SD = 9.11). In patients with immediate DIEP reconstruction, hypoperfused areas identified by SPY angiography increased risk of necrosis ( P = .012). Approximately 50% of both partial thickness and full thickness necrosis patients had concerns on SPY angiography. Former smokers in the full thickness necrosis group had more pack years than those without necrosis (9 vs .65 pack years, P = .035)., Conclusion: In patients receiving NSM with DIEP flap reconstruction, those with hypoperfusion on SPY angiography and longer smoking history had higher necrosis rates. This supports the continued used of SPY angiography and the role of pre-operative counseling in former smokers with increased pack years on their risk of necrosis and the role of preventative measures in the perioperative setting., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Non-Hispanic Black women have lower breast cancer incidence but twice the mortality of non-Hispanic White women. Recent data suggest that the overall survival difference may not be observed in older women. This study aims to determine overall survival in women aged ≥70 years with operable breast cancer by race and ethnicity and factors contributing to overall survival., Methods: The National Cancer Database was queried to identify women aged ≥70 years with stage 0-III breast cancer from 2004 to 2018. Patients were separated by race and ethnicity: non-Hispanic White, non-Hispanic Black, Hispanic, and Other. To examine overall survival, a Cox proportional hazards model was created, and overall survival was calculated using the Kaplan-Meier method., Results: There were 304,345 eligible patients. The mean age was 76.8 years (standard deviation 5.5 years), and most were non-Hispanic White (85.2%), had Medicare (86.8%), had hormone receptor-positive breast cancer (78.7%), and underwent partial mastectomy (64.5%). Compared with non-Hispanic White women, non-Hispanic Black women had a higher prevalence of stage III disease (10.8% vs 7.5%, P < .001) and triple-negative breast cancer (16.7% vs 8.7% P < .001), and a longer time to treatment initiation (39.2 vs 32.3 days, P < .001). Median follow-up was 5.38 years (interquartile range: 3.83-7.46 years). Non-Hispanic Black women had the lowest median survival time compared with non-Hispanic White women (9.7 vs 10.4 years, P < .001). After adjusting for insurance type, receptor status, stage, comorbidity, time to treatment, and facility type, there was no increased risk of death for non-Hispanic Black patients (hazard ratio: 0.99, 95% confidence interval: 0.96-1.01, P = .29)., Conclusion: Although overall survival was lower in older non-Hispanic Black women, this difference resolved on multivariate modeling, suggesting that other factors likely influence overall survival for this cohort., Competing Interests: Conflict of Interest/Disclosure The authors have no conflicts of interest or disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Current guidelines do not recommend routine sentinel node biopsy (SLNB) for ductal carcinoma in situ (DCIS), except in the setting of mastectomy or microinvasive disease. This study aimed to evaluate national SLNB utilization in women undergoing upfront mastectomy for DCIS, identify predictors of SLNB utilization, and determine the percentage with a positive SLNB., Methods: A retrospective cohort analysis was performed using the NCDB of women with clinical DCIS who underwent upfront mastectomy between 2012 and 2017. Demographic and clinicopathologic variables were compared between patients who underwent SLNB and those who did not. Multivariate logistic regression models were used to identify factors associated with SLNB utilization and positive SLNB., Results: About 38,973 patients met inclusion criteria: 34,231 (88%) underwent SLNB and 4742 (12%) had no surgical axillary staging. Most patients were age 50-69 (51%), non-Hispanic White (71%), with private insurance (66%). On multivariate analysis, older patients were less likely to receive SLNB (P < .01), while patients with higher grade DCIS were more likely to undergo SLNB (P < .01). In those who underwent SLNB (n = 34,231), only 1,149 (3.4%) had nodal involvement. Non-Hispanic Black patients had increased odds of a positive SLNB (P < .01), while those with estrogen receptor positive disease were less likely to be node positive (OR 0.68, P < .001)., Conclusions: While 88% of patients had a SLNB, only 3.4% were found to be node positive. Given this low rate, it is reasonable to consider SLNB omission in select patients with low grade, hormone receptor positive DCIS undergoing upfront mastectomy., Competing Interests: Disclosures All authors have no disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Axillary assessment in breast cancer is key to determining an upfront surgery or neoadjuvant chemotherapy (NAC) approach. We investigated the false-negative rate (FNR) of axillary-node ultrasound-guided core-needle biopsy (US-CNBx) and the surgical management of pN ​+ ​patients., Methods: This single-institution study from 2010 to 2020 included patients with benign findings on US-CNBx and upfront surgery. Statistical analyses were performed via t-tests and chi-squared tests., Results: 95 axillae met inclusion, 23 were pN+, resulting in a US-CNBx FNR of 24.2 ​%. pN ​+ ​patients more frequently had cT2-T3 tumors vs pN0 patients (43.5 ​% vs 27.8 ​%, p ​= ​0.03). Of the 23 ​pN ​+ ​patients, 9 underwent breast-conserving surgery (BCS) and 14 underwent mastectomy. In those with BCS, 7 had 1-2 positive nodes, 2 had ≥3 nodes; 3 received an ALND. In those with mastectomies, 12 had 1-2 positive nodes, 2 had ≥3 positive nodes; 6 received an ALND., Conclusion: In this cohort, US-CNBx had a FNR of 24.2 ​%. pN ​+ ​patients had a greater frequency of cT2-cT3 tumors, therefore clinicians should be cognizant of potential occult nodal disease despite negative CNBx when deciding management., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest No conflicts of interest.

Objective: To assess the accuracy, quality, and readability of patient-focused breast cancer websites using expert evaluation and validated tools., Background: Ensuring access to accurate, high-quality, and readable online health information supports informed decision-making and health equity but has not been recently evaluated., Methods: A qualitative analysis on 50 websites was conducted; the first 10 eligible websites for the following search terms were included: "breast cancer," "breast surgery," "breast reconstructive surgery," "breast chemotherapy," and "breast radiation therapy." Websites were required to be in English and not intended for healthcare professionals. Accuracy was evaluated by 5 breast cancer specialists. Quality was evaluated through the DISCERN questionnaire. Readability was measured using 9 standardized tests. Mean readability was compared with the American Medical Association and National Institutes of Health 6th grade recommendation., Results: Nonprofit hospital websites had the highest accuracy (mean = 4.06, SD = 0.42); however, no statistical differences were observed in accuracy by website affiliation ( P = 0.08). The overall mean quality score was 50.8 ("fair"/"good" quality) with no significant differences among website affiliations ( P = 0.10). Mean readability was at the 10th grade reading level, the lowest being for commercial websites with a mean 9th grade reading level (SD = 2.38). All websites exceeded the American Medical Association- and National Institutes of Health-recommended reading level by 4.4 levels ( P < 0.001). Websites with higher accuracy tended to have lower readability levels, whereas those with lower accuracy had higher readability levels., Conclusion: As breast cancer treatment has become increasingly complex, improving online quality and readability while maintaining high accuracy is essential to promote health equity and empower patients to make informed decisions about their care., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Current management strategies for early-stage triple-negative breast cancer (TNBC) include upfront surgery to determine pathologic stage to guide chemotherapy recommendations, or neoadjuvant chemotherapy (NAC) to de-escalate surgery, elucidate tumor response, and determine the role of adjuvant chemotherapy. However, patients who receive NAC with residual pathological nodal (pN) involvement require axillary lymph node dissection (ALND) as they are Z11/AMAROS ineligible. We aimed to evaluate the impact of NAC compared with upfront surgery on pN status and ALND rates in cT1-2N0 TNBC., Methods: The National Cancer Database (NCDB) was queried for women with operable cT1-2N0 TNBC from 2014 to 2019. Demographic, clinicopathologic, and treatment data were collected. Multivariable linear regression analysis was performed to assess the odds of pN+ disease and undergoing ALND., Results: Overall, 55,624 women were included: 26.9% (n = 14,942) underwent NAC and 73.1% (n = 40,682) underwent upfront surgery. The NAC cohort was younger (mean age 52.9 vs. 61.3 years; p < 0.001) with more cT2 tumors (71.6% vs. 31.0%; p < 0.001), and had lower ALND rates (4.3% vs. 5.5%; p < 0.001). The upfront surgery cohort was more likely to have one to three pathologically positive nodes (12.1% vs. 6.5%; odds ratio [OR] 2.37, 95% confidence interval (CI) 2.17-2.58; p < 0.001) but there was no difference in the likelihood of ALND (OR 1.1, 95% CI 0.99-1.24; p = 0.08)., Conclusion: Patients who underwent upfront surgery were more likely to be pN+; however, ALND rates were similar between the two cohorts. Thus, the use of NAC does not result in a higher odds of ALND and the decision for NAC should be individualized and based on modern guidelines and systemic therapy benefits., (© 2024. Society of Surgical Oncology.)

Purpose: Neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) allows for assessment of tumor pathological response and has survival implications. In 2017, the CREATE-X trial demonstrated survival benefit with adjuvant capecitabine in patients TNBC and residual disease after NAC. We aimed to assess national rates of NAC for cT1-2N0M0 TNBC before and after CREATE-X and examine factors associated with receiving NAC vs adjuvant chemotherapy (AC)., Methods: A retrospective cohort study of women with cT1-2N0M0 TNBC diagnosed from 2014 to 2019 in the National Cancer Database (NCDB) was performed. Variables were analyzed via ANOVA, Chi-squared, Fisher Exact tests, and a multivariate linear regression model was created., Results: 55,633 women were included: 26.9% received NAC, 52.4% AC, and 20.7% received no chemotherapy (median ages 53, 59, and 71 years, p < 0.01). NAC utilization significantly increased over time: 19.5% in 2014-15 (n = 3,465 of 17,777), 27.1% in 2016-17 (n = 5,140 of 18,985), and 33.6% in 2018-19 (n = 6,337 of 18,871, p < 0.001). On multivariate analysis, increased NAC was associated with younger age (< 50), non-Hispanic white race/ethnicity, lack of comorbidities, cT2 tumors, care at an academic or integrated-network cancer program, and diagnosis post-2017 (p < 0.05 for all). Patients with government-provided insurance were less likely to receive NAC (p < 0.01). Women who traveled > 60 miles for treatment were more likely to receive NAC (p < 0.01)., Conclusion: From 2014 to 2019, NAC utilization increased for patients with cT1-2N0M0 TNBC. Racial, socioeconomic, and access disparities were observed in who received NAC vs AC and warrants interventions to ensure equitable care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The "Going Flat" movement became widely publicized in 2016 and provides information and support to women who choose to forego post-mastectomy breast reconstruction (PMBR). The objectives of this study were to evaluate temporal trends in PMBR to ascertain the potential impact of this movement and assess which factors are associated with going flat., Methods: A retrospective cohort analysis was performed using the NCDB of women with non-metastatic breast cancer who underwent mastectomy between 2004 and 2019. Trends in going flat after mastectomy were examined and stratified by age (< 50, 50-69, ≥ 70). A multivariate logistic regression model was used to identify factors associated with going flat., Results: 650,983 patients met the inclusion criteria: 244,201 (37.5%) underwent PMBR and 406,782 (62.5%) went flat. Among women < 70, rates of going flat steadily decreased from 2004 to 2015 and then stabilized after 2015, coinciding with the rise of the "Going Flat" movement. In multivariate analysis, non-White race, older age, increasing comorbidities, government provided insurance, treatment at a community program, radiotherapy, and adjuvant chemotherapy were associated with a higher likelihood of going flat (p < 0.001)., Conclusion: In the first 2 years after the "Going Flat" movement, the number of women going flat after mastectomy has stabilized in women < 70 for the first time in over a decade. These trends suggest that the social and cultural impact of this movement may have contributed to the stabilization of PMBR rates., (© 2023. Society of Surgical Oncology.)

Background: Endocrine resistant metastatic disease develops in ~ 20-25% of hormone-receptor-positive (HR+) breast cancer (BC) patients despite endocrine therapy (ET) use. Upregulation of HER family receptor tyrosine kinases (RTKs) represent escape mechanisms in response to ET in some HR+ tumors. Short-term neoadjuvant ET (NET) offers the opportunity to identify early endocrine escape mechanisms initiated in individual tumors., Methods: This was a single arm, interventional phase II clinical trial evaluating 4 weeks (± 1 week) of NET in patients with early-stage HR+/HER2-negative (HER2-) BC. The primary objective was to assess NET-induced changes in HER1-4 proteins by immunohistochemistry (IHC) score. Protein upregulation was defined as an increase of ≥ 1 in IHC score following NET., Results: Thirty-seven patients with cT1-T3, cN0, HR+/HER2- BC were enrolled. In 35 patients with evaluable tumor HER protein after NET, HER2 was upregulated in 48.6% (17/35; p = 0.025), with HER2-positive status (IHC 3+ or FISH-amplified) detected in three patients at surgery, who were recommended adjuvant trastuzumab-based therapy. Downregulation of HER3 and/or HER4 protein was detected in 54.2% of tumors, whereas HER1 protein remained low and unchanged in all cases. While no significant volumetric reduction was detected radiographically after short-term NET, significant reduction in tumor proliferation rates were observed. No significant associations were identified between any clinicopathologic covariates and changes in HER1-4 protein expression on multivariable analysis., Conclusion: Short-term NET frequently and preferentially upregulates HER2 over other HER family RTKs in early-stage HR+/HER2- BC and may be a promising strategy to identify tumors that utilize HER2 as an early endocrine escape pathway., Clinical Trial Registry: Trial registration number: NCT03219476., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: High-volume hospitals (HVHs) are associated with improved overall survival (OS) following surgery for breast cancer compared with low-volume hospitals (LVHs). We examined this association in patients age ≥ 80 years and described patient and treatment characteristics associated with HVHs., Patients and Methods: The National Cancer Database was queried for women age ≥ 80 years who underwent surgery for stage I-III breast cancer between 2005 and 2014. Hospital volume was defined as the average number of cases during the year of the patient's index operation and the year prior. Hospitals were categorized into HVHs and LVHs using penalized cubic spline analysis of OS. A cutoff of ≥ 270 cases/year defined HVHs., Results: Among 59,043 patients, 9110 (15%) were treated at HVHs and 49,933 (85%) at LVHs. HVHs were associated with more non-Hispanic Black and Hispanic patients, earlier stage disease (stage I 54.9% vs. 52.6%, p < 0.001), higher rates of breast-conserving surgery (BCS) (68.3% vs. 61.4%, p < 0.001), and adjuvant radiation (37.5% vs. 36.1%, p = 0.004). Improved OS was associated with surgery at a HVH (HR 0.85, CI 0.81-0.88), along with receipt of adjuvant chemotherapy (HR 0.73, CI 0.69-0.77), endocrine therapy (HR 0.70, CI 0.68-0.72), and radiation (HR 0.66, CI 0.64-0.68)., Conclusions: Among patients with breast cancer age ≥ 80 years, undergoing surgery at a HVH was associated with improved OS. Patients who completed surgery at HVHs had earlier stage disease and more commonly received adjuvant radiation when appropriate. Processes of care at HVHs should be identified to improve outcomes in all settings., (© 2023. Society of Surgical Oncology.)

Although surgery of the breast and axilla is generally well-tolerated by patients, the breast surgeon recognizes that complications can occur even when operating with experience on the lowest risk patients. The operative repertoire ranges from breast conserving surgery, mastectomy (including skin-sparing and nipple-sparing types), to modified radical mastectomy, with each procedure carrying a different expected surgical morbidity. Patients and families who are fully informed of potential complications before their operation describe greater trust in their surgeon and are better able to co-manage complications with the surgical team, when they occur., Competing Interests: Disclosure No relevant disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In DCIS, ER status is an important marker. The utility of concomitant PR testing remains unclear., Methods: A single-institution retrospective cohort study was performed with a comparative analysis of the NCDB to assess annual cost-savings with omission of routine PR testing. National Medicare payment standards determined PR staining costs to be $124.92., Results: 150 institutional DCIS cases with receptor data were identified. 104 (69%) were ER+/PR+, 16 (11%) were ER+/PR-, and none were ER-/PR+. Omission of routine PR testing would have resulted in $18,738 saved annually. Within the NCDB, 34,100 DCIS cases had receptor data: 29,277 (85.9%) patients were ER+, and 26,008 (76%) were both ER/PR+. 211 (0.6%) patients were ER-/PR+. Annual national cost-savings with omission of routine PR-testing would have been $4.3 million., Conclusion: PR testing for DCIS should be reserved only for patients with ER- DCIS undergoing breast conservation to determine the utility of adjuvant endocrine therapy., Competing Interests: Declaration of competing interest The authors have no financial or non-financial interests to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Declarations of interests We declare no competing interests.

Objective: Test the effectiveness of benchmarked performance reports based on existing discharge data paired with a statewide intervention to implement evidence-based strategies on breast re-excision rates., Background: Breast-conserving surgery (BCS) is a common breast cancer surgery performed in a range of hospital settings. Studies have demonstrated variations in post-BCS re-excision rates, identifying it as a high-value improvement target., Methods: Wisconsin Hospital Association discharge data (2017-2019) were used to compare 60-day re-excision rates following BCS for breast cancer. The analysis estimated the difference in the average change preintervention to postintervention between Surgical Collaborative of Wisconsin (SCW) and nonparticipating hospitals using a logistic mixed-effects model with repeated measures, adjusting for age, payer, and hospital volume, including hospitals as random effects. The intervention included 5 collaborative meetings in 2018 to 2019 where surgeon champions shared guideline updates, best practices/challenges, and facilitated action planning. Confidential benchmarked performance reports were provided., Results: In 2017, there were 3692 breast procedures in SCW and 1279 in nonparticipating hospitals; hospital-level re-excision rates ranged from 5% to >50%. There was no statistically significant baseline difference in re-excision rates between SCW and nonparticipating hospitals (16.1% vs. 17.1%, P =0.47). Re-excision significantly decreased for SCW but not for nonparticipating hospitals (odds ratio=0.69, 95% confidence interval=0.52-0.91)., Conclusions: Benchmarked performance reports and collaborative quality improvement can decrease post-BCS re-excisions, increase quality, and decrease costs. Our study demonstrates the effective use of administrative data as a platform for statewide quality collaboratives. Using existing data requires fewer resources and offers a new paradigm that promotes participation across practice settings., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Primary breast neuroendocrine tumors (BNETs) represent < 1% of breast cancers. Diagnosing BNETs can be challenging, and a limited amount of cohort data currently exists in literature. We aimed to describe primary BNET characteristics, treatment modalities, and survival outcomes through the National Cancer Database (NCDB)., Methods: A retrospective cohort analysis was performed using the NCDB from 2004 to 2017. BNET cases were compared with patients with invasive ductal carcinoma (IDC). A matched IDC cohort was created by matching patient age, race, and disease stage. Kaplan-Meier analysis was performed, and hazard ratios (HR) were calculated through the bootstrap sampling method., Results: A total of 1389 BNET and 1,967,401 IDC cases were identified. When compared with IDC patients, BNET patients were older, had more comorbidities, and were more often male (p < 0.01). BNETs were larger, higher grade, and more frequently hormone receptor negative (p < 0.01). While BNET patients were treated with surgery and radiotherapy (p < 0.01) less often compared with IDC patients, they presented at later disease stage (p < 0.001) and received systemic treatment more frequently (53.5% vs. 40%, p < 0.01). Patients with BNET had increased mortality compared with the matched IDC cohort: stage 1 HR 1.8, stage 2 HR 2.0, stage 3 HR 1.8, and stage 4 HR 1.5 (p < 0.001 for all)., Conclusion: Patients with BNET tend to present at higher clinical stages, are more frequently hormone receptor negative, and have inferior overall survival compared with patients with IDC. Further treatment strategies and studies are needed to elucidate optimal therapies to maximize patient outcomes., (© 2022. Society of Surgical Oncology.)

Background: Despite an aging population, there are no established treatment guidelines for women with ductal carcinoma in situ (DCIS) age ≥80. Here we describe national treatment patterns and survival outcomes in older women with DCIS., Patients and Methods: Women age ≥80 diagnosed with DCIS from 2005 to 2014 were identified using the National Cancer Database. χ2, Fisher's exact test, and logistic regression models were used to identify factors influencing receipt of breast surgery, and Kaplan-Meier method and Cox proportional hazard models were used to evaluate overall survival (OS)., Results: A total of 6,070 women with DCIS met inclusion criteria, of which the majority (98%) received surgery. Receipt of surgery was independently associated with age <90. OS was higher for those who received surgery compared to those who did not (HR 2.2 [1.72-2.83] P < .001)., Conclusion: The vast majority of patients age ≥80 with DCIS in the National Cancer Database received primary surgical management, which was associated with a significant OS benefit. Considering comorbidities and patient fitness, surgical resection should be considered for all patients age ≥80 who are suitable operative candidates., (Copyright © 2022. Published by Elsevier Inc.)

Background: Clinical trials have demonstrated methods to minimize the risk of breast cancer-related lymphedema while preserving regional control. We sought to determine the percent lifetime-risk of breast cancer-related lymphedema that surgeons and radiation oncologists discuss with patients before axillary interventions., Methods: A nationwide survey of surgeons and radiation oncologists was performed from July to August 2020. Participants were asked to identify what number they discuss with patients when estimating the percent lifetime-risk of breast cancer-related lymphedema after different axillary interventions., Results: Six hundred and eighty surgeons and 324 radiation oncologists responded (14% response rate). While the estimated rate after sentinel lymph node biopsy was clinically similar between surgeons and radiation oncologists, statistically surgeons quoted a higher percent lifetime-risk (5.7% vs 5.0%, P = .03). Surgeons estimated significantly higher rates of breast cancer-related lymphedema compared with radiation oncologists (P < .001) for axillary lymph node dissection (21.8% vs 17.5%), sentinel lymph node biopsy with regional nodal irradiation (14.1% vs 11.2%), and axillary lymph node dissection with regional nodal irradiation (34.8% vs 26.2%)., Conclusion: There is variability in the estimated rates of breast cancer-related lymphedema providers discuss with patients. These findings highlight the need for physician education on the current evidence of percent lifetime-risk of breast cancer-related lymphedema to provide patients with accurate estimates before axillary interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: There are no established treatment guidelines for women with breast cancer aged ≥80 despite increasing representation in the US population. Here we identify national treatment patterns and survival outcomes in women with stage I-III invasive breast cancer., Patients and Methods: Women age ≥80 diagnosed with stage I-III invasive breast cancer (IBC) were identified from 2005-2014 in the National Cancer Database. χ 2 , Fisher's exact test, and logistic regression models were used to identify factors influencing receipt of breast surgery, and Cox proportional hazard models were used to evaluate overall survival (OS)., Results: A total of 62,575 women with IBC met inclusion criteria, of which the majority received surgery (94%). Receipt of surgery was associated with White race, age <90, lower stage, and fewer comorbidities. OS was higher for those who received surgery compared to those who did not (HR 3.3 [3.18-3.46] P < .001). Molecular subtype analysis demonstrated improved survival with receipt of surgery or radiation for all subtypes, as well as improved survival with chemotherapy for those with triple negative breast cancer., Conclusion: The vast majority of breast cancer patients aged ≥80 in the National Cancer Database with IBC received primary surgical management, which was associated with a significant OS benefit. Due to this finding, surgical resection should be considered for all patients ≥80 who are suitable operative candidates., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess national practice patterns in axillary management in patients undergoing upfront mastectomy and examines what guides provider recommendations., Methods: A national case-based survey study was performed of surgeons and radiation oncologists from July to August 2020. Surgeons were identified through the American Society of Breast Surgeons (ASBrS) after review and approval by the ASBrS Research Committee, and radiation oncologists were identified through an institutional database. Both descriptive and comparative statistical analyses were performed., Results: Overall, 994 providers responded-680 surgeons and 314 radiation oncologists. Surgeons were older and in practice longer (p < 0.05) and treated a higher percentage of breast patients (81% vs. 40%, p < 0.001). Most surgeons were hospital-employed (43%), whereas most radiation oncologists were in private practice (40%; p < 0.001). Fifty-two percent of surgeons routinely send sentinel lymph nodes (SLNs) for frozen section (52%) during mastectomy, of which 78% proceed directly to axillary lymph node dissection (ALND) if positive. There was significant variability in treatment recommendations between the two groups among the hypothetical cases (p < 0.001). In the setting of low disease burden in the SLNs, > 30% of surgeons recommended ALND, while radiation oncologists recommend axillary radiotherapy over axillary clearance (p < 0.001)., Conclusion: There is significant heterogeneity in the management of the axilla in mastectomy patients with pathologically positive SLNs, both between and among surgeons and radiation oncologists. Efforts should be made to assist both groups in identifying de-escalation opportunities to ensure that mastectomy patients with positive SLNs are treated appropriately., (© 2021. Society of Surgical Oncology.)

Background: Signet ring cell breast carcinoma (SRCBC) is a rare variant of invasive lobular carcinoma and there are no large series characterizing its long-term prognosis., Materials and Methods: The NCDB was queried from 2004-2016 to identify SRCBC patients. Patients were excluded if they had non-invasive tumors, multiple malignancies, or incomplete surgical data. Univariate analysis was performed utilizing chi-squared and Fischer's Exact tests. Kaplan-Meier and Cox proportional hazard models were used for survival analysis., Results: 324 patients met inclusion criteria. Patients were mostly White (75.3%), ≥50 years of age (88.2%), female (98.5%), and had a low Charlson-Deyo score (82.7%). 34.5% had Stage IV disease and 78.1% had ER+ tumors. In patients with non-Stage IV disease, 91.5% received surgery: 49.5% had lumpectomy and 50.5% underwent mastectomy. Radiation therapy was used in 40.7% (71.4% with lumpectomy and 35.8% with mastectomy) and 50% received chemotherapy. Significant differences in unadjusted overall survival were seen at 5 and 10 years based on stage (P < 0.001). On multivariate analysis, ER+ patients showed an improved survival (HR 0.5, P < 0.01) but there was no difference in survival if ER+ patients received endocrine therapy (ET) (HR 0.9, P = 0.57). Non-metastatic patients who underwent surgery had improved overall survival compared to those that did not (HR 0.5, P = 0.02), but there was no survival difference based upon type of breast operation (P = 0.8)., Conclusion: SRCBC frequently presents at an advanced stage. While ER+ patients appear to have improved survival, there was no clear survival benefit to receiving ET in ER+ patients., Competing Interests: Declarations of competing interests None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Breast cancer incidence in women aged ≥70 years is steadily increasing, and many are choosing to undergo postmastectomy breast reconstruction (PMBR). We aimed to identify factors associated with PMBR, describe reconstruction types, and assess postoperative mortality and re-admission rates in women ≥70 years of age., Methods: The National Cancer Database (NCDB) was examined between 2004 and 2015 for women aged ≥70 years with breast cancer who underwent mastectomy. Statistical analysis was performed by χ 2 tests and multivariate logistic regression to select the best models for predicting PMBR and if patients underwent contralateral prophylactic mastectomy (CPM) with reconstruction., Results: A total 73,973 patients met inclusion criteria and 4,552 (6.1%) underwent PMBR, of which 25% had a CPM. 48% had implant reconstruction, 36.2% underwent autologous reconstruction, and 15.1% received combination reconstruction. PMBR was more likely to be performed in patients who were White, had fewer comorbidities, were treated in the Northeast metropolitan areas, and with lower tumor stage (P < .001). CPM was more likely to be performed in patients who were White and treated in community hospitals in rural areas in the South and West. (P < .05). Although 30-day readmission rates were higher in PMBR patients (3.5% vs 2.8%, P < .001), 30 and 90-day mortality rates were lower: 0.03 and 0.2% vs 0.3 and 0.9% (P < .001)., Conclusion: Although it is understandable that intrinsic tumor characteristics influence the role of PMBR, further research and interventions should be aimed to eliminate the differences that are seen in patient race and geographic location. Readmission and postop mortality rates are overall low and comparable to that of younger patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Communication of statistics and probability is challenging in the cancer care setting. The objectives of this study are to evaluate a novel approach to cancer communication through the use of a computer assessment of patient health numeracy. Methods: We conducted a pilot study of the Computer Adapted Test of Numeracy Understanding in Medicine Instrument (CAT-NUMi) before the cancer treatment consultation for women with stage 0-3 breast cancer. Patient outcomes included the interpersonal processes of care (IPC) and the decisional conflict scale. We evaluated clinician use of numeric information in the cancer consultation and assessed feasibility outcomes from the clinician and patient perspective. Results: Patient participants ( n  = 50) had a median (interquartile range) age of 51 years (46-61), 70% were English speaking, and 30% Spanish speaking. Decisional conflict was low with a mean (standard deviation [SD]) decisional conflict score of 17.4 (12.3). The lack of clarity score (range 1-5) on the IPC was low (mean, SD),1.70 (0.71), indicating clear communication. Clinicians more often used percentages in communicating prognosis among those with higher numeracy scores (median, range): high (2, 0-8), medium (1, 0-7), and low (0, 0-8); p  = 0.04. The patient experience of taking the CAT-NUMi was rated as very good or excellent by 65%, fair by 33%, and poor by 2% of patients. Conclusion: Screening for health numeracy with a short computer-based test may be a feasible strategy to optimize clear communication in the cancer treatment consultation. Further studies are needed to evaluate this strategy across cancer treatment clinical settings and populations.

Purpose of Review: Breast cancer incidence and mortality increase with age. Older patients (≥ 70) are often excluded from studies. Due to multiple factors, it is unclear whether this population is best-treated using standard guidelines. Here, we review surgical management in older women with breast cancer., Recent Findings: Geriatric assessments can guide treatment recommendations and aid in predicting survival and quality of life. Surgery remains a principal component of breast cancer treatment in older patients, though differences exist compared with younger women, including higher mastectomy rates and evidence-based support of omission of post-lumpectomy radiation or axillary dissection in subsets of patients. In those forgoing surgical management, there is increased use of endocrine therapy. Hospice is also a valuable element of end-of-life care. Physicians should utilize geriatric assessment to make treatment recommendations for older breast cancer patients, including omission of radiation therapy, alterations to standard surgeries, or enrollment in hospice care.

No clear standard treatment guidelines exist for older women with breast cancer. In this study we aimed to examine the practice patterns and treatment outcomes of women ≥80 years old with invasive breast cancer. A retrospective chart review at a single academic institution was performed of 124 women diagnosed with stage I to III invasive breast cancer aged ≥80 years between 2005 and 2014. Median age of diagnosis was 84 years. Fifty-nine of the cancers (48%) were detected using mammography. One hundred twelve patients (90%) underwent surgery. There was no difference in comorbidities between the surgical and nonsurgical group (P = .800). In multivariate analysis, age was predictive of receiving surgery (P < .001). Overall survival probability was higher for those who received hormonal therapy (P = .002), radiation therapy (P = .041), and those with lower-stage tumors (P = .018). Surgery was not predictive of survival. It is important to consider comorbidities, complications and, longevity when determining whether elderly women diagnosed with breast cancer benefit from surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Reduction mammaplasty is one of the most common procedures performed by plastic surgeons. Previous studies demonstrated that most plastic surgeons do not require preoperative mammography prior to reduction mammaplasty. The incidental discovery of malignant or high-risk lesions in breast reduction specimens may preclude the possibility of breast-conserving surgery. The purpose of this study was to examine the factors associated with discussion of preoperative mammography with reduction mammaplasty patients., Methods: About 638 consecutive patients were identified between January 2000 and December 2010 who underwent reduction mammaplasty. Clinicopathologic and treatment information was collected. Factors associated with discussion of preoperative mammography prior to surgery were compared., Results: Of 638 patients, the median age was 36 (range 18-77) with 44% ≥40. Approximately half (56.0%) were White and 37.5% were African-American. The use of mammography was discussed in 43.3% of patients and completed in 41.5%. On final pathology, eight patients (1.3%) had high-risk lesions and two (0.3%) demonstrated malignancy (1 DCIS, 1 invasive). Of these 10 patients, two were under the age of 40 and four had preoperative mammograms. Factors associated with mammography discussion were age ≥40, White race, the presence of comorbidities, family history of breast cancer, prior breast surgery, prior breast biopsy, history of breast cancer (all P < 0.0001) and tobacco use (P = 0.04)., Conclusions: Due to the potential risk of invasive cancer and high-risk lesions in the final surgical specimen, preoperative mammography should be discussed with selected patients by plastic surgeons, particularly those who fall within national screening guidelines., (© 2019 Wiley Periodicals, Inc.)

Preoperative or neo-adjuvant chemotherapy in the management of breast cancer is a treatment approach that has gained in popularity in recent years. However, it is unclear if the treatment paradigms often employed for patients treated with surgery first hold true for those treated with preoperative chemotherapy. The role of sentinel node biopsy and the data supporting its use is different for those with clinically negative and clinically positive nodes prior to chemotherapy. For clinically node-negative patients, sentinel node biopsy after neo-adjuvant chemotherapy may be appropriate. For those node-positive patients whose axillary disease resolves clinically, the false-negative rate of the sentinel node biopsy is high. However, there are measures that can reduce that rate. After surgery, the radiation oncologist is often faced with complicated decisions surrounding the optimal radiotherapy in this setting. Tailoring radiation plans based on chemotherapy response holds promise and is the subject of ongoing clinical trials. In the accompanying article, we review the current literature on both surgery and radiation in axillary management and describe the interplay between these two treatment modalities. This highlights the need for multidisciplinary management in making treatment decisions for patients treated in this manner., (© 2018 Wiley Periodicals, Inc.)

Purpose: To examine the relationship between patient and tumor characteristics, patterns of breast cancer care, and 5-year survival among a population-based cohort of elderly women with incident breast cancer, with a special focus on identifying sources of socioeconomic (SES) disparities in outcomes., Methods: We identified women with newly diagnosed breast cancer in 2006-2009 from the Surveillance and Epidemiology End Result study linked with Medicare claims. A Classification and Regression Tree (CART) model was applied to 13 individual indicators of neoadjuvant and adjuvant breast cancer treatment, tumor characteristics, and patient sociodemographic variables to identify patterns with the greatest discriminant value in predicting 5-year survival. We subsequently examined the extent to which these patterns varied by the patient's SES., Results: Survival probabilities associated with the 18 unique CART-identified patterns ranged from 22 to 87%. The number of positive axillary nodes was the best single discriminator between high and lower survival outcomes. The most common discriminant factor among patterns with poor (< 25%) survival was the absence of radiation treatment, followed by the presence of comorbidities, tumor size > 2 cm, and no breast surgery. Relative to high SES women, poor women were nearly four times (12.3% vs. 3.2%, p < 0.001) as likely to be classified in the pattern associated with worse survival, and less likely (31.7% vs. 52.9%, p = 0.04) to receive the pattern associated with the greatest survival., Conclusions: Greater adoption of effective patterns of care could improve survival of elderly women with incident breast cancer overall, and reduce SES disparities therein.

Purpose: Although users of aromatase inhibitors have higher total fracture risk in some randomized trials, little is known about their risk outside of clinical trials or in older higher-risk cohorts., Methods: In a population-based retrospective cohort study, we identified all older US Medicare D prescription drug insurance plan-enrolled women who had initial breast cancer surgery in 2006-2008 and began hormonal therapy (an aromatase inhibitor (AI) or tamoxifen) within the subsequent year. Total nonvertebral and hip fractures through 2012 were identified using a validated algorithm. The association of fracture outcomes with hormonal therapy type was assessed using competing risk regression models that accounted for differences in measured baseline covariates. Treatment assignment bias was reduced using inverse probability of treatment weighting computed from propensity scores., Results: Among 23,378 women taking hormonal therapy (23.2% aged 80 or over), there were 3000 total and 436 hip fractures. Although AI users were younger and had lower comorbidity, after propensity score weighting, these and other covariates were balanced. Total nonvertebral risk was higher for users of AIs compared with tamoxifen, HR 1.11 (1.02-1.21), but the small increase in risk for hip fracture was not statistically significant, HR 1.04 (0.84-1.30)., Conclusions: Although total nonvertebral fracture risk was higher among AI users, differences in hip fractures were not significant in a large population-based cohort of older women., Implications for Cancer Survivors: Use of aromatase inhibitors by older women is associated with high risk for nonvertebral fracture that is increased compared with use of tamoxifen. Fracture risk should be assessed among patients taking these medications.

Background: Dengue is identified as serious vector born infectious disease by WHO, threating around 2.5 billion people around the globe. Pakistan is facing dengue epidemic since 1994 but 2010 and 2011 dengue outbreaks were worst. During 2011 dengue outbreak 22,562 cases were reported and 363 died due to this fatal infection in Pakistan. In this study, Lahore District was chosen as it was severely affected in 2011 dengue outbreak with 14,000 reported cases and 300 deaths. There is no vaccine developed yet for the disease control, so only effective early warning, prevention and control measures can reduce the potential disease risk., Methods: This study proposes a method for detecting spatial autocorrelation of temporal dynamics of disease using Local Index of Spatial Autocorrelation (LISA) using three temporal indices: (a) how often the dengue cases occur, frequency index; (b) how long the epidemic wave prevails, duration index; (c) how significant dengue cases occur in successive periods, severity index. Overlay analysis of LISA value for each temporal index resulted in eight risk types., Results: The mapping of spatio-temporal risk indices and their overlay analysis identified that 10.6% area of Lahore (184.3km 2 and population density 119,110persons/km 2 ) had high values for frequency, duration, and severity index (p<0.05) and 16% area (having 25% population) is at potential risk of dengue., Conclusion: Spatial risk identification by using local spatial-autocorrelation helps in identifying other possible causes of disease risk and further strategic planning for prevention and control measures., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Mutations in BRCA1 or BRCA2 genes results in an elevated risk for developing both breast and ovarian cancers over the lifetime of affected carriers. General surgeons may be faced with questions about surgical risk reduction and survival benefit of prophylactic surgery., Methods: A systematic literature review was performed using the electronic databases PubMed, OVID MEDLINE, and Scopus comparing prophylactic surgery vs observation with respect to breast and ovarian cancer risk reduction and mortality in BRCA mutation carriers., Results: Bilateral risk-reducing mastectomy provides a 90% to 95% risk reduction in BRCA mutation carriers, although the data do not demonstrate improved mortality. The reduction in ovarian and breast cancer risks using risk-reducing bilateral salpingo-oophorectomy has translated to improvement in survival., Conclusions: Clinical management of patients at increased risk for breast cancer requires consideration of risk, patient preference, and quality of life., (Copyright © 2016 Elsevier Inc. All rights reserved.)