Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors.

The microbiome impacts human health and disease. Until recently, human breast tissue and milk were presumed to be sterile. Here, we investigated the presence of microbes in the nipple aspirate fluid (NAF) and their potential association with breast cancer. We compared the NAF microbiome between women with a history of breast cancer (BC) and healthy control women (HC) using 16S rRNA gene amplicon sequencing. The NAF microbiome from BC and HC showed significant differences in community composition. Two Operational Taxonomic Units (OTUs) showed differences in relative abundances between NAF collected from BC and HC. In NAF collected from BC, there was relatively higher incidence of the genus Alistipes. By contrast, an unclassified genus from the Sphingomonadaceae family was relatively more abundant in NAF from HC. These findings reflect the ductal source DNA since there were no differences between areolar skin samples collected from BC and HC. Furthermore, the microbes associated with BC share an enzymatic activity, Beta-Glucuronidase, which may promote breast cancer. This is the first report of bacterial DNA in human breast ductal fluid and the differences between NAF from HC and BC. Further investigation of the ductal microbiome and its potential role in breast cancer are warranted.

Multivitamin/multimineral supplements for cancer prevention: implications for primary care practice.

There is a popular belief that multivitamin and mineral (MVM) supplements can help prevent cancer and other chronic diseases. Studies evaluating the effects of MVM supplements on cancer risk have largely been observational, with considerable methodologic limitations, and with conflicting results. We review evidence from the few available randomized, controlled trials that assessed the effects of supplements containing individual vitamins, a combination of a few select vitamins, or complete MVM supplements, with a focus on the recent Physicians' Health Study II (PHS II). PHS II is a landmark trial that followed generally healthy middle-aged and older men (mean age 64 years) who were randomized to daily MVM supplementation for a mean duration of 11 years. Men taking MVMs experienced a statistically significant 8% reduction in incidence of total cancer (hazard ratio [HR]: 0.92; 95% confidence interval [CI]: 0.86-0.998; p = 0.04). Men with a history of cancer derived an even greater benefit: cancer incidence was 27% lower with MVM supplementation versus placebo in this subgroup (HR: 0.73; 95% CI: 0.56-0.96; p = 0.02). Positive results of PHS II contrast with randomized studies of individual vitamins or small combinations of vitamins, which have largely shown a neutral effect, and in some cases, an adverse effect, on cancer risk. The results of PHS II may have a considerable public health impact, potentially translating to prevention of approximately 68 000 cancers per year if all men were to use similar supplements, and to an even greater benefit with regard to secondary prevention of cancer.

The impact of screening tools on diagnosis of chronic obstructive pulmonary disease in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is frequently misdiagnosed or undiagnosed, which can delay disease management interventions. PURPOSE: The Screening, Evaluating and Assessing Rate CHanges of diagnosing respiratory conditions in primary care 1 (SEARCH1) study assessed whether screening using the COPD Population Screener (COPD-PS) questionnaire to detect COPD risk factors and symptoms, with or without a handheld spirometer (copd-6) to detect airflow limitation, can increase yields of COPD diagnosis and respiratory-related clinician actions in primary care. DESIGN: A prospective, multi-center, pragmatic, comparative-effectiveness, cluster-randomized study conducted from September 2010 to October 2011 (data analyzed from December 2011 to January 2013). PARTICIPANTS: Men and women aged ≥40 years visiting their participating primary care practice for any reason. INTERVENTION: Practices were randomized to three study arms: COPD-PS + copd-6, COPD-PS alone, and usual care (no interventions). No practices received any specific education about COPD or its diagnosis. MAIN OUTCOME MEASURES: The primary endpoint was yield of new clinical COPD diagnosis; the secondary endpoint was yield of respiratory-related clinician actions. RESULTS: Of 9,704 patients enrolled, 8,770 had no prior COPD diagnosis and were included in endpoint analyses. Both interventions significantly increased COPD diagnostic yield over 8 weeks. Compared with a mean yield of 0.49% (0.13%) (controls), yields were 1.07% (0.20%) (OR=2.20, 95% CI=1.26, 3.84, p=0.006) and 1.16% (0.22%) (OR=2.38, 95% CI=1.38, 4.13, p=0.002) for COPD-PS and COPD-PS+copd-6 study arms, respectively. Respiratory-related clinician actions were not significantly different across study arms. CONCLUSIONS: Office-based assessment can significantly increase COPD diagnosis by primary care physicians. Future trials must evaluate whether screening can improve outcomes for patients with COPD.

Improving early-stage diagnosis and management of COPD in primary care.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, but it often remains undetected in its mild and moderate forms. Patients frequently remain undiagnosed and untreated until the disease has become severe and debilitating, greatly impacting their quality of life. Primary care physicians (PCPs) are most often the first point of contact, and therefore they are in the best position to identify patients at risk of COPD in the early stages. Consequently, they play a critical role in the management of the disease, particularly smoking cessation. One of the earliest symptoms is activity-related dyspnea and subsequent exercise intolerance, often compensated for by reduction in physical activity. This review addresses the approaches used to identify COPD in the primary care setting, including simple tools such as handheld spirometers and questionnaires. A recent study demonstrated that, compared with usual care, use of the COPD Population Screener questionnaire alone and in combination with the copd-6 handheld spirometer significantly improved the odds of referral of patients with suspected COPD for pulmonary function testing or to a pulmonologist. Identification of patients suspected of having the disease and differentiation of COPD from asthma are important in order that treatment can be initiated in the mild stages to slow or prevent disease progression and reduce the risk of exacerbations. The review also discusses the evidence to date on pharmacologic treatment using short-acting and long-acting anticholinergics and ß2-agonists, and nonpharmacologic interventions, such as smoking cessation, pulmonary rehabilitation, and influenza and pneumococcal vaccination in patients with mild and moderate COPD.

Weight loss reduces breast ductal fluid estrogens in obese postmenopausal women: a single arm intervention pilot study.

BACKGROUND: Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women. METHODS: We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage. RESULTS: Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%). CONCLUSIONS: Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Identifying chronic obstructive pulmonary disease in primary care of urban underserved patients: tools, applications, and challenges.

Among urban low-income and minority patients with compromised access or low adherence to primary care, exacerbations of unrecognized but symptomatic moderate to severe chronic obstructive pulmonary disease (COPD) cause avoidable emergency room visits and hospitalizations. Detection and management of COPD before a first exacerbation reduces morbidity and disability, forestalls cardiorespiratory complications, improves health-related quality of life, and reduces health care costs. However, current efforts in ascertainment and care of COPD have insufficiently improved outcomes in underserved groups. Effective COPD care requires access to detection and management resources: screening tools to identify who may have COPD, spirometric diagnosis, smoking cessation assistance, vaccinations, stage-appropriate pharmacotherapy, and rehabilitation. This article describes recent advances in tools suitable for assisting COPD identification in primary care practices and discusses their applications in urban underserved populations. The validated COPD Population Screener is readily understood by patients, self-scored, available online (www.copdscreener.com), and usable in community outreach as well as primary care settings. Symptom-based risk stratification with a validated questionnaire provides a rational trigger targeting limited spirometry resources to patients most likely to have COPD. Case finding is the first step of COPD management to reduce its individual and public health burden.

Biomarker analysis on breast ductal lavage cells in women with and without breast cancer.

Recent studies show that morphology based analysis of ductal lavage specimens failed to detect many cancers in women with breast cancer. Such an observation raises doubts about the potential role of ductal lavage in an individual's risk assessment and early detection of breast cancer. We hypothesize that biomarker-based analysis using markers of malignancy field defects including DNA 5c exceeding rate (DNA 5cER) and G-actin might provide a more reliable test for breast cancer risk. The study was performed in 2 phases, the training and validation phase. For the training phase, 36 Chinese women were recruited (13 with breast cancer, 8 with intraductal papilloma and 15 with benign breast diseases). The validation phase included 10 women with cancer and 7 women without cancer. Ductal lavage samples were processed by the ThinPrep technique and evaluated by morphology followed by biomarker analysis using laser scan cytometry (LSC) for G-actin and DNA5cER. In the training phase, biomarker analysis was performed on the 67% (24 of 36) of samples that had over 100 epithelial cells. The sensitivity of DNA5cER was 90% with a specificity of 100%, and G-actin was 100% and 93%, respectively. By contrast, the sensitivity and specificity obtained by cytology alone were 67% and 93%, respectively. Similar results were obtained from the small validation study. Quantitative analysis of biomarkers for G-actin and DNA5cER is feasible and useful in distinguishing benign from malignant breast disease on archived ductal lavage slides. Further studies are warranted to determine the value of these biomarkers in prospective trials.