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The aim of this study was to show for the first time that low-frequency 3D-transmitted ultrasound tomography (3D UT, volography) can differentiate breast tissue types using tissue properties, accurately measure glandular and ductal volumes in vivo, and measure variation over time. Data were collected for 400 QT breast scans on 24 women (ages 18–71), including four (4) postmenopausal subjects, 6–10 times over 2+ months of observation. The date of onset of menopause was noted, and the cases were further subdivided into three (3) classes: pre-, post-, and peri-menopausal. The ducts and glands were segmented using breast speed of sound, attenuation, and reflectivity images and followed over several menstrual cycles. The coefficient of variation (CoV) for glandular tissue in premenopausal women was significantly larger than for postmenopausal women, whereas this is not true for the ductal CoV. The glandular standard deviation (SD) is significantly larger in premenopausal women vs. postmenopausal women, whereas this is not true for ductal tissue. We conclude that ducts do not appreciably change over the menstrual cycle in either pre- or post-menopausal subjects, whereas glands change significantly over the cycle in pre-menopausal women, and 3D UT can differentiate ducts from glands in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Although improvements in breast cancer detection and treatment have significantly increased survival, important questions related to breast cancer risk, prognosis, and survivorship remain. This brief report describes the Health of Women (HOW) Study® methodology and characterizes the participants who completed the My Health Overview and My Breast Cancer modules. Methods: The HOW Study® was a collection of cross-sectional, web-based modules designed to survey a large number of participants with and without breast cancer. Results: A total of 42,540 participants completed the My Health Overview module, of whom 13,285 (31.2%) reported a history of breast cancer. The majority of participants were white (94.3%), female (99.5%), married (74.1%), college educated (73.2%), post-menopausal (91.1%), parous (68.8%), and reported breastfeeding their children (56.0%). A total of 11,670 participants reported a history of breast cancer in the My Breast Cancer module. The majority of survivors reported on their primary breast cancer and were diagnosed over the age of 40 years (83.5%), had either Stage I or Stage II breast cancer (63.1%), and were treated with surgery (98.8%), radiation (64.8%), and/or chemotherapy (62.3%). Conclusions: The HOW Study® provides an innovative framework for collecting large amounts of epidemiological data in an efficient and minimally invasive way. Data are publicly available to researchers upon request. Implications for Cancer Survivors: The HOW Study® can be leveraged to answer important questions about survivorship, and researchers are encouraged to utilize this new data source. [ABSTRACT FROM AUTHOR]

Introduction: For all clinical providers in healthcare, decision-making is a critical feature of everything they do. Every day physicians engage in clinical decision-making where knowledge, evidence, experience, and interpretation of clinical data are used to produce decisions, yet, it is fair to say that most do not have an explicit insight or understanding of this complex process. In particular, few will have training in teaching and assessing the cognitive and affective factors that underlie clinical decisionmaking. Methods: To foster an increased awareness and understanding of these factors, the Dalhousie Critical Thinking Program was established with the mandate to develop and deliver curriculum for critical thinking in the 4-year undergraduate program. To assist teaching faculty with the goal and objectives of the program, the Teaching and Assessing Critical Thinking Program (TACT) was introduced. Results: Using the dual process model as a platform for decision-making, this program introduces general principles of critical thinking and provides tools to teach learners how to strengthen their critical thinking skills. To offer flexible learning, an online approach was chosen for delivery of the program. Conclusion: To date, we have offered eleven iterations of Part 1 to a total of 261 participants and six iterations of Part 2 to a total of 89 participants. Evaluations show the online approach to content delivery was well received and the content to be of practical use. [ABSTRACT FROM AUTHOR]

Background: The link between Epstein-Barr Virus (EBV) and breast cancer (BC) etiology remains unclear. We utilized the Health of Women (HOW) Study® to understand the association between infectious mononucleosis (IM), a surrogate for EBV infection, and invasive BC. Methods: The HOW Study® was a web-based survey of BC risk factors with > 40, 000 participants; 183 had IM at < 10 years old, 3, 654 had IM between 10 and 22 years old, 764 had IM at > 22 years old, and 17, 026 never developed IM. Of these 21, 627 women, 2093 had Stages I–III BC and 14, 143 were cancer-free. Binary logistic regression ascertained the association between IM and invasive BC risk by controlling for confounders. Results: A history of IM was associated with a lower likelihood of developing invasive BC compared to women who did not develop IM (adjusted OR = 0.83, 95% CI 0.72–0.94). That finding was driven by women who had IM between 10 and 22 years old (adjusted OR = 0.83, 95% CI 0.72–0.97) albeit no linear association between age at developing IM and breast cancer (p-trend > 0.05). Women who had IM between 10 and 22 years old were less likely to develop estrogen receptor positive (ER+ ; adjusted OR = 0.84, 95% CI 0.71–0.99) or hormone receptor positive (HR+ ; adjusted OR = 0.86, 95% CI 0.73–1.01) BC. There was no association between IM and ER− or HR− BC. Conclusion: In the HOW Study®, women diagnosed with IM between the ages of 10 and 22 had a lower risk of developing invasive BC compared to women who never developed IM. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ (DCIS) represents approximately 20–25% of newly diagnosed breast cancers. DCIS is treated by surgery and possibly radiotherapy. Chemotherapy is only used as adjuvant or neoadjuvant therapy but not as primary therapy. The present study investigated the intraductal administration of Ciclopirox (CPX) formulated in nanosuspensions (NSs) or nanoparticles (NPs) to treat DCIS locally in a Fischer 344 rat model orthotopically implanted with 13762 Mat B III cells. Slow converting esterase responsive CPX prodrugs (CPDs) were successfully synthesized at high purity (> 95%) by directly acetylating the hydroxyl group or by appending a self-immolative linker between CPX and a phenolic ester. Direct esterification CPDs were not sufficiently stable so self-immolative CPDs were formulated in NSs and NPs. Prodrug release was evaluated from poly(lactic-co-glycolic acid) NPs, and CPD4 demonstrated the slowest release rate with the rank order of CPD2 (R = methyl) > CPD3 (R = t-butyl) > CPD4 (R = phenyl). Intraductally administered CPX NS, CPD4 NS, and an innovative mixture of CDP4 NS and NPs (at 1 mg CPX equivalent/duct) demonstrated significant (p < 0.05) in vivo anti-tumor efficacy compared with immediate release (IR) CPX NS and non-treated controls. CPX mammary persistence at 6 h and 48 h after CPD4 NS or NP administration was also greater than after the immediate release CPX NS. A strong correlation between CPX mammary persistence and efficacy is demonstrated. In conclusion, nanoformulations utilizing a slow releasing/slow bioconverting CPX prodrug delivery strategy resulted in significant dose de-escalation (~ five fold) while maintaining anti-tumor efficacy. [ABSTRACT FROM AUTHOR]

The primary and secondary benefits of tamoxifen as adjuvant therapy in women with hormone-receptor-positive breast cancer are substantial: a 1% decrease in the risk of death each year for 10 years with each additional year of treatment during the first 5 years. Considerable data, however, indicate that these benefits are lost to many patients because of treatment nonadherence. Nonadherence is examined within the framework of the Common-Sense Model of Self-Regulation to describe patients' models of disease and treatment that organize their thinking and behavior, and the crucial role of the practitioner in addressing and altering these models. Common patient education and social communications about patients' hormone-receptor-positive breast cancer and tamoxifen treatment promote an acute disease paradigm in which cancer occurs within specific locations and is either present or absent. We recommend that clinicians communicate the concepts of hormone-receptor-positive breast cancer as follows: i. a non-dichotomous systemic disorder entailing a treatment goal of homeostasis and disease quiescence and ii. a disorder undetectable by currently available tests in subclinical states. Equally important, the clinician can provide a comprehensive picture of the well-documented secondary effects of tamoxifen, noting in particular the beneficial effects. Specific action plans, grounded in individual patient understanding, can be developed and reinforced, in an ongoing process that validates and integrates patient values and goals as they change over time. [ABSTRACT FROM AUTHOR]

Background: Shared decision-making (SDM) occurs when a patient partners with their oncologist to integrate personal preferences and values into treatment decisions. A key component of SDM is the elicitation of patient preferences and values, yet little is known about how and when these are elicited, communicated, prioritized, and documented within clinical encounters.Methods: This cross-sectional study evaluated nationwide data collected by CancerCare to better understand current patterns of SDM between patients and their oncology clinicians. Patient surveys included questions about the importance of quality-of-life preferences and discussions regarding quality-of-life priorities with their clinicians. Clinician surveys included questions about the discussion of quality-of-life priorities and preferences with patients, the effect of quality-of-life priorities on treatment recommendations, and quality-of-life priority documentation in practice.Results: Patient survey completers (n = 320; 33% response rate) were predominantly women (95%), had a diagnosis of breast cancer (59%), or were receiving active cancer treatment (59%). Clinician survey completers (n = 112; 5% response rate) predominately identified as hematologists or oncologists (66%). Although 67% of clinicians reported knowing their patients' personal quality-of-life priorities and preferences before finalizing treatment plans, only 37% of patients reported that these discussions occurred before treatment initiation. Most patients (95%) considered out-of-pocket expenses important during treatment planning, yet only 59% reported discussing out-of-pocket expenses with their clinician before finalizing treatment plans. A majority of clinicians (52%) considered clinic questionnaires as feasible to document quality-of-life priorities and preferences.Conclusions: Patients and clinicians reported that preferences related to quality-of-life should be considered in treatment decision making, yet barriers to SDM, preference elicitation, and documentation remain. [ABSTRACT FROM AUTHOR]

Objective: Acute myeloid leukemia (AML) is experiencing a therapeutic renaissance due to the heightened biomedical understanding of AML and patient-focused drug development (PFDD). Many AML patients now live long-term with the side effects of treatment. This study documents the prevalence and severity of AML treatment-related side effects. Methods: A national cross-sectional survey designed with the Leukemia & Lymphoma Society assessed patients' experiences with short-term (nausea/vomiting, diarrhea, hair loss, mouth sores, infection, rash) and long-term (organ dysfunction, chemobrain, fatigue, neuropathy) treatment side effects. Patient and caregiver participants rated side effect severity (none-severe). Results: Survey participants (n = 1182) were mostly female (65%), AML patients (76%), and had undergone chemotherapy (94%). Eighty-seven per cent of participants reported severe short-term effects, and 33% reported severe long-term effects of treatment. Only 11% of respondents did not have any severe effects. Hair loss and fatigue were the most common severe short- and long-term side effects (78%, 33%). There was a moderate correlation between having short- and long-term adverse effects (r = 0.41, p < 0.001). Caregivers were more likely than patients to report severe organ dysfunction, fatigue, and neuropathy (p-values < 0.05). Conclusions: Survivors experience a high burden of side effects from AML treatments highlighting the need for the development of less toxic therapies. Differences in patients' and caregivers' experiences illustrate the importance of sampling from diverse sources to understand the full burden of AML treatment, and the need for less toxic drugs. This study informs patients, patient-advocacy groups, clinicians, and regulators about AML treatment burdens and provides the community with information to inform PFDD. [ABSTRACT FROM AUTHOR]

Ductal carcinoma in situ is the most commonly diagnosed early stage breast cancer. The efficacy of intraductally delivered poly(ethylene glycol)‐doxorubicin (PEG‐DOX) nanocarriers, composed of one or more DOX conjugated to various PEG polymers, was investigated in an orthotopic ductal carcinoma in situ‐like rat model. In vitro cytotoxicity was evaluated against 13762 Mat B III cells using MTT assay. The orthotopic model was developed by inoculating cancer cells into mammary ducts of female Fischer 344 retired breeder rats. The ductal retention and in vivo antitumour efficacy of two of the six nanocarriers (5 kDa PEG‐DOX and 40 kDa PEG‐(DOX)4) were investigated based on in vitro results. Mammary retention of DOX and PEG‐DOX nanocarriers was quantified using in vivo imaging. Histopathologic effects of DOX and PEG‐DOX nanocarriers on mammary ductal structure were also investigated. Cytotoxicities of small linear PEG‐DOX nanocarriers (5 and 10 kDa) were not different from DOX whereas larger PEG‐DOX nanocarriers showed reduced potency. The order of mammary retention was 40 kDa PEG‐(DOX)4 > 5 kDa PEG‐DOX >> DOX, in normal and tumour‐bearing rats. Intraductally administered PEG‐DOX nanocarriers and DOX were effective in reducing tumour incidence and increasing survival rate, with no significant differences found among the three treatment groups. However, nanocarriers administered intravenously at the same doses were not effective, and intraductally administered free DOX caused severe local toxicity. Intraductal administration of PEG‐DOX nanocarriers is effective and less toxic than that of free DOX, as well as IV DOX/PEG‐DOX. Furthermore, PEG‐DOX nanocarriers demonstrate the added benefit of prolonging DOX ductal retention, which would necessitate less frequent dosing. PEG‐DOX nanocarriers possess cytotoxic potency in vitro. They not only exert antitumour effects in vivo but also have the beneficial capabilities of prolonging mammary retention and reducing local adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: In low- to middle-income countries (LMICs), most breast cancers present as palpable lumps; however, most palpable lumps are benign. We have developed artificial intelligence–based computer-assisted diagnosis (CADx) for an existing low-cost portable ultrasound system to triage which lumps need further evaluation and which are clearly benign. This pilot study was conducted to demonstrate that this approach can be successfully used by minimally trained health care workers in an LMIC country. Patients and Methods: We recruited and trained three nonradiologist health care workers to participate in an institutional review board–approved, Health Insurance Portability and Accountability Act–compliant pilot study in Jalisco, Mexico, to determine whether they could use portable ultrasound (GE Vscan Dual Probe) to acquire images of palpable breast lumps of adequate quality for accurate computer analysis. Images from 32 women with 32 breast masses were then analyzed with a triage-CADx system, generating an output of benign or suspicious (biopsy recommended). Triage-CADx outputs were compared with radiologist readings. Results: The nonradiologists were able to acquire adequate images. Triage by the CADx software was as accurate as assessment by specialist radiologists, with two (100%) of two cancers considered suspicious and 30 (100%) of 30 benign lesions classified as benign. Conclusion: A portable ultrasound system with CADx software can be successfully used by first-level health care workers to triage palpable breast lumps. These results open up the possibility of implementing practical, cost-effective triage of palpable breast lumps, ensuring that scarce resources can be dedicated to suspicious lesions requiring further workup. [ABSTRACT FROM AUTHOR]

Purpose: Until recently, people with metastatic breast cancer (MBC) had a very poor prognosis. New treatment approaches have prolonged the time that people with MBC live, but their quality of life has received less attention. Consequently, the needs and concerns across financial, vocational, psychological, social, and physical domains in MBC patients are poorly understood—particularly regarding the collateral damage or longer-term, life-altering impacts of MBC and its treatments. This study’s aims were to characterize MBC-related collateral damage, identify groups most likely to experience collateral damage, and examine its associations with psychological health, illness management, and health behaviors.Methods: Participants (N = 515) with MBC were recruited from Dr. Susan Love Research Foundation’s Army of Women® and other advocacy organizations. Participants completed questionnaires of MBC-related collateral damage, depressive symptoms, anxiety, self-efficacy for managing oncologic treatments and physical symptoms, sleep, and physical activity.Results: Eight domains of MBC-related collateral damage, as well as MBC-related benefit finding, were reliably characterized. Concerns about mortality/uncertainty were most prominent. Participants also endorsed high levels of benefit finding. Participants younger than 50 years, with limited financial resources, or with children under 18 at home reported the most collateral damage. Collateral damage was associated significantly with compromised psychological health, lower illness management efficacy, and poorer health behaviors, beyond sociodemographic and medical characteristics.Conclusions: Subgroups of MBC patients report long-term, life-altering consequences of MBC and its treatments, which relate to important health outcomes. Clinical implications and recommendations are discussed. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden.Methods: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden.Results: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time.Conclusion: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time. [ABSTRACT FROM AUTHOR]

Purpose: In low- to middle-income countries (LMICs), most breast cancers present as palpable lumps; however, most palpable lumps are benign. We have developed artificial intelligence–based computer-assisted diagnosis (CADx) for an existing low-cost portable ultrasound system to triage which lumps need further evaluation and which are clearly benign. This pilot study was conducted to demonstrate that this approach can be successfully used by minimally trained health care workers in an LMIC country. Patients and Methods: We recruited and trained three nonradiologist health care workers to participate in an institutional review board–approved, Health Insurance Portability and Accountability Act–compliant pilot study in Jalisco, Mexico, to determine whether they could use portable ultrasound (GE Vscan Dual Probe) to acquire images of palpable breast lumps of adequate quality for accurate computer analysis. Images from 32 women with 32 breast masses were then analyzed with a triage-CADx system, generating an output of benign or suspicious (biopsy recommended). Triage-CADx outputs were compared with radiologist readings. Results: The nonradiologists were able to acquire adequate images. Triage by the CADx software was as accurate as assessment by specialist radiologists, with two (100%) of two cancers considered suspicious and 30 (100%) of 30 benign lesions classified as benign. Conclusion: A portable ultrasound system with CADx software can be successfully used by first-level health care workers to triage palpable breast lumps. These results open up the possibility of implementing practical, cost-effective triage of palpable breast lumps, ensuring that scarce resources can be dedicated to suspicious lesions requiring further workup. [ABSTRACT FROM AUTHOR]

Background: The human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit. Methods: We examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data. Results: We found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid. Conclusions: Our results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas. [ABSTRACT FROM AUTHOR]

Dr. Susan Love Research Foundation is committed to performing and advancing research that will lead to the discovery of what causes cancer to develop in the human breast. As part of this effort, the Foundation hosted the 8th International Symposium on the Breast in Santa Monica, Calif., Feb. 19 to Feb. 21, 2015. More than 120 forward-thinking clinical researchers, epidemiologists, pathologists, basic scientists, translational investigators, and breast cancer advocates from six countries attended this year's conference, 'Using Next Generation Science to Understand the Normal Breast and the Development of Cancer.' The highlights from this year's symposium are summarized in this report. [ABSTRACT FROM AUTHOR]

Importance: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD.Objective: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor.Design, Setting, and Participants: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers.Interventions: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152).Main Outcomes and Measures: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures.Results: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants).Conclusions and Relevance: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden.Trial Registration: clinicaltrials.gov Identifier: NCT00235716. [ABSTRACT FROM AUTHOR]

IMPORTANCE Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS Over the mean (SD) follow-up of 2.27 (1.22) years, participants receiving alpha tocopherol had slower decline than those receiving placebo as measured by the ADCS-ADL. The change translates into a delay in clinical progression of 19% per year compared with placebo (approximately 6.2 months over the follow-up period). Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations" with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). ADCS-ADL Inventory Baseline score, mean (SD) Least squares mean (SE) change from baseline Mean change difference compared with placebo (95% CI) Vitamin E (n = 140) 57.20 (14.38) -13.81 (1.11) 3.15 (0.92 to 5.39) Memantine (n = 142) 57.77 (13.78) -14.98 (1.10) 1.98 (-0.24 to 4.20) Vitamin E + Memantine (n = 139) 57.16 (13.59) -15.20 (1.11) 1.76 (-0.48 to 4.00) Placebo (n = 140) 56.93 (13.61) -16.96 (1.11) CONCLUSIONS AND RELEVANCE Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00235716 [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of nanocarrier molecular size and shape on breast duct retention in normal rats using a non-invasive optical imaging method. Methods: Fluorescein-labeled PEG nanocarriers of different molecular weights and shapes (linear, two-arm, four-arm, and eight-arm) were intraductally administered (50 nmol) to female Sprague-Dawley rats. Whole body images were obtained non-invasively. Fluorescence intensities (i.e., amount remaining in duct) were plotted against time to estimate the nanocarrier ductal retention half-lives (t). Plasma samples were taken and the pharmacokinetics (Tmax, Cmax) of absorbed nanocarriers was also assessed. Results: The t of linear 12, 20, 30, 40, and two-arm 60 kDa nanocarriers were 6.7 ± 0.9, 16.1 ± 4.1, 16.6 ± 3.4, 21.5 ± 2.7, and 19.5 ± 6.1 h, whereas the four-arm 20, 40, and eight-arm 20 kDa had t of 9.0 ± 0.5, 11.5 ± 1.9, and 12.6 ± 3.0 h. The t of unconjugated fluorescein was significantly lower (14.5 ± 1.4 min). The Tmax for 12, 40, 60 kDa nanocarriers were 1, 24, and 32 h, respectively, and only 30 min for fluorescein. Conclusions: Since normal breast ducts are highly permeable, the use of nanocarriers may be helpful in prolonging ductal retention of diagnostic and/or therapeutic agents. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LM's). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries. [ABSTRACT FROM AUTHOR]

The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression. [ABSTRACT FROM AUTHOR]

The intraductal approach is particularly appealing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understanding of the anatomy of the ductal system as well as novel techniques to leverage the access accorded by the intraductal approach, researchers are actively exploring how ductal lavage, ductoscopy, and intraductal infusion of therapeutic agents may enhance breast cancer treatment. Both cytologic and molecular diagnostics continue to improve, and work is ongoing to identify the most effective diagnostic biomarkers for DCIS and cancer, although optimal targeting of the diseased duct remains an important consideration. Ductoscopy holds potential in detection of occult intraductal lesions, and ductoscopically guided lumpectomy could increase the likelihood of a more comprehensive surgical excision. Exciting pilot studies are in progress to determine the safety and feasibility of intraductal chemotherapy infusion. These studies are an important starting point for future investigations of intraductal ablative therapy for DCIS, because as our knowledge and techniques evolve, it is likely that DCIS may be the target most amenable to treatment by intraductal therapy. If such studies are successful, these approaches will allow an important and meaningful transformation in treatment options for women diagnosed with DCIS. [ABSTRACT FROM AUTHOR]

Over the last 25 years, there has been a growing body of basic science, modeling, and clinical data suggesting that the peri-operative period in the treatment of primary breast cancer is dynamic and can be manipulated to improve long-term outcomes. Clinical data have demonstrated early peaks of hazards for recurrence and emphasized the relationship of these to peri-operative events. More recently, clinical trial data with surgical oophorectomy at different times in the menstrual cycle, peri-operative progesterone, and anti-inflammatory drugs suggest that interventional studies are particularly well justified, given the increasing recognition of the costs both financially and clinically of current systemic regimens. [ABSTRACT FROM AUTHOR]

Fiberoptic ductoscopy (FDS)-guided intraductal biopsy is a minimally invasive technique developed to obtain pathologic diagnoses for patients with spontaneous nipple discharge. We performed biopsies of 53 intraductal lesions from March 2006 to April 2007 followed by surgical microdochectomy. FDS-guided intraductal biopsy was shown to be a minimally invasive, safe, and convenient technique with a high ability (90.6%) to get adequate samples. Twenty-seven solitary papillomas, 12 multiple intraductal papilloma, five ductal hyperplasia, three ductal carcinoma in situ, and one invasive ductal carcinoma were diagnosed. Compared with conventional microdochectomy, FDS-guided intraductal biopsy can significantly increase the detection rate of solitary papilloma (40.7% versus 92.6%, p < 0.05). It should be a routine procedure after intraductal lesion found by screening FDS. Since it would underestimate all multiple intraductal papilloma and some (50%) cancer, microdochectomy is inevitable if biopsies show atypical ductal hyperplasia. [ABSTRACT FROM AUTHOR]

Researchers are using the intraductal approach to advance breast cancer risk assessment, prevention, diagnosis, and treatment. Procedures and technologies that can access and interrogate the ductal-alveolar systems include nipple aspiration, ductal lavage and ductoscopy. Ductoscopic papillectomy, ductoscopic margin evaluation, and intraductal therapy are considered promising investigational and innovative treatments. These techniques are used to explore the biology of the normal breast; collect and analyze breast fluid and cells to identify biomarkers that can be used in breast cancer detection and risk assessment; and to identify new ways to find and administer therapeutic and/or preventive agents to the breast tissue. This report summarizes the latest research findings in these areas, presented at The 6th International Symposium on the Intraductal Approach to Breast Cancer in 2009. [ABSTRACT FROM AUTHOR]

Ductal lavage is a technique that samples the contents of breast ducts for research into the biology of breast cancer. Enthusiasm for this method has declined because of technical challenges associated with the procedure. These include: difficulty in duct cannulation, high levels of subject discomfort, and an inability to confirm perforation. As part of a larger institutional review board (IRB)-approved study, consenting healthy women underwent ductal lavage of 3–4 ducts in one breast. Intranipple lidocaine was administered before duct cannulation. Ductoscopy was performed prior to catheterization and high-definition ultrasound was used for imaging during the lavage procedure. Pain scores were recorded at 24 hours and 2 weeks. Subjects were asked to return in 6 months for a repeat of the procedure. Ductoscopy was performed prior to lavage under real-time ultrasound 308 times in 107 subjects. There were 280 confirmed ducts (90.9%) and 21 perforations (6.8%), while seven (2.3%) were indeterminate. Subjects reported minimal discomfort, and 91% reported a 0 (0–10 range) pain score 2 weeks after the procedure. The retention rate was 90% at 6 months. The injection of lidocaine directly into the nipple greatly increases the feasibility of duct cannulation and improves subject comfort. Confirmation of duct cannulation and lavage can be documented with ductoscopy and ultrasound imaging. These procedures can be added to ductal lavage to facilitate its use as a research tool. [ABSTRACT FROM AUTHOR]

By 2010, the majority of approximately 1.5 million annual new cases of breast cancer will be diagnosed in women in countries with limited resources. Public health approaches to medical problems emphasize the importance of practical, limited toxicity and very inexpensive interventions. While clinical trials in Western countries are testing the concept of breast cancer prevention, they are not defining useful public health approaches. Early detection of breast cancer using mammography, while effective, is a high-technology, expensive approach. Adjuvant systemic and radiation therapies are increasingly expensive; careful consideration of efficacy and cost-efficacy data appear warranted. Public health perspectives thus suggest that many current “standard” approaches to breast cancer in Western countries cannot help the majority of women in the world. [ABSTRACT FROM AUTHOR]

The American Community Survey (ACS) is a continuous measurement survey program designed to replace the census long form sample. While the census sample provides detailed socioeconomic data once a decade, the ACS will provide these data annually using a questionnaire that largely mirrors the census long form. This paper examines operational data in Bronx County, one of 36 ACS test counties, and finds the ACS superior to the census on two important measures of data quality. First, applying the minimal data requirement for inclusion of a long form in the census sample, ACS questionnaires were significantly more likely than the long forms to meet this threshold. Second, the level of nonresponse to items on the ACS was often one-half the census level. The ACS and census have sharply divergent goals and operational methods that affect data quality. The primary objective of the census is a population count for reapportionment and redistricting; collecting long form information is a secondary goal. In contrast, the primary objective of the ACS is to estimate the characteristics of an area based on answers to all items on the survey. Operationally, the census follows up every nonresponding household, using a pool of minimally trained, temporary workers. In comparison, the ACS follows up only one-in-three nonresponding households, using a permanent cadre of professional interviewers. This results in superior nonresponse follow-up in the ACS, with lower levels of non-sampling error, even in more difficult-to-enumerate high poverty areas of the Bronx. The ACS is to be fully implemented in July 2004, pending Congressional funding. With detailed socioeconomic data available annually from the ACS, the 2010 census would then be able to focus primarily on a population headcount. The paper concludes by discussing operational aspects of the ACS that must be improved, including increasing its visibility, for the survey to be accepted as an integral part of the nation's data collection system. [ABSTRACT FROM AUTHOR]

The Facial Recognition Test (Benton, Hamsher, Varney, & Spreen, 1983;Benton, Sivan, Hamsher, Varney, & Spreen, 1994) was examined in an age-,education- and gender-stratified sample of 346 healthy older adults. Internalconsistency reliability estimates were .72 for the Long Form (FRLF), .53 forthe Short Form, and .69 for a new short form. Mean FRLF scores did not changeover a 1-year interval ( p > .5), and the stability estimate was .71( n = 100). The first of the methods below yielded the highest correlationbetween estimated and obtained FRLF scores in cross-validation ( n = 67): (1) multiple regression based on oral reading and demographics, (2)multiple regression based on age, education and gender, and (3) mean scoresby age group. [ABSTRACT FROM AUTHOR]

This report describes the methods and sample characteristics of a neuropsychologicalstudy of the elderly conducted by the Geriatric Research, Education and ClinicalCenter of the Department of Veterans Affairs Medical Center in Minneapolis,Minnesota. The goal of the study was to provide normative data, internal consistencyand 1-year reliability estimates, and validated methods of estimating expectedperformance level. Thirty-one cognitive measures and a demographic questionnairewere administered to an age-, education-, and gender-stratified sample ( N = 349) and a validation sample ( N = 70). After 1 year, 104of the participants were retested. Relative to published, nationally basednormative data, the stratified sample showed performance levels that rangedfrom average to high average across the five tests examined. [ABSTRACT FROM AUTHOR]