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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 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.

Received June 28, 2001; revision received September 24, 2001; accepted October 1, 2001. Breast carcinoma arises in the epithelial cells lining the milk ducts and lobules that comprise the ductal system of the breast. Ductal lavage is a minimally invasive office procedure performed on women who are considered to be at high risk for breast carcinoma to collect breast ductal epithelial cells for cytologic analysis to provide further risk stratification. The procedure involves the insertion of a microcatheter approximately 1.5 cm into a nipple orifice after topical anesthesia; lavaging the cannulated ductal system with normal saline; and analyzing the collected lavage effluent for the presence of normal, atypical, or malignant breast ductal cells. The purpose of this commentary is to review the data supporting breast ductal cytology as a tool to provide high-risk women with individualized information regarding their risk of developing breast carcinoma, and to provide a discussion of clinical management options based on the results of ductal lavage cytology.

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.

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.

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.

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.

The current breast cancer diagnostic methods rely on identification of the tumor mass and therefore have limited success for detecting early lesions in which preventive measures could effectively be carried out. We propose a novel approach using ductal lavage technique, coupled with biomarker profile analysis on the fluid and cells obtained. This approach facilitates the detection of malignant or premalignant lesions in individuals who have undetectable tumor masses. We hypothesis that the development of breast cancer is preceded by molecular field disease changes, and therefore cells obtained from any area of the duct will signal the biochemical and molecular changes associated with carcinogenesis. To test this hypothesis, we first performed a molecular mapping study. Ductal epithelial cells obtained from cancerous and non-cancerous ducts were collected from several mastectomy samples. Molecular analysis including analysis of proliferation marker Ki67 and methylation of RAR-B were performed.

Obesity and adulthood weight gain, operating through production of estrone in adipose tissue, inflammation, and obesity-related growth factors, increase breast cancer risk after menopause. Many studies have determined the systemic effects of excess adipose tissue on plasma and serum-based biomarkers, but few studies have determined the localized impact on biomarkers contained in breast ductal fluid. We are currently conducting a pilot 12-week diet and exercise weight-loss intervention among overweight postmenopausal women to evaluate changes in ductal fluid as a result of the intervention. To date, five women completed the study. We successfully obtained breast ductal fluid both before and after the intervention from four of the five women. Fluid was transferred into tubes and frozen in a -80° freezer. We are currently conducting assay measurements of hormones and biomarkers contained in ductal fluid. We observed changes in body composition and exercise parameters as a function of the intervention. Specifically, a 12% decrease in BMI (body-mass index), a 14% decrease in body fat mass, a 28% increase in aerobic fitness and 28% increase in muscle-strength occurred compared to baseline intervention measurements, among the women who completed the study. Our plans are to enroll five additional women, finish analyzing the ductal fluid biomarkers, and apply for a larger grant to expand the study.