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Two studies were conducted to examine the hypothesis that noradrenergic activity is a cause of the anticipatory nausea associated with cancer chemotherapy. In the first study concentrations of plasma 3-methoxy-4-hydroxyphenyl-glycol (MHPG) on day 1 of cycle 5 of initial chemotherapy were significantly higher in patients with than without anticipatory nausea. To determine whether elevated MHPG reflected a clinically significant causative role for noradrenergic activity in anticipatory nausea, we conducted a randomized, double-blind, placebo-controlled, crossover trial of clonidine for anticipatory nausea. At a dose of clonidine that produced significant side effects and reductions of plasma MHPG, anticipatory nausea was improved only marginally. These studies do not support a causative role for noradrenergic activity in anticipatory nausea that can be reduced by clonidine with an acceptable therapeutic index.

Cancer-related fatigue (CRF) is a common complication of cancer and its treatment that can significantly impair quality of life. Although the specific mechanisms remain poorly understood, inflammation is now considered to be a distinct component of CRF in addition to effects of depression, anxiety, insomnia, and other factors. One key biological pathway that may link inflammation and CRF is indoleamine 2,3-dioxygenase (IDO). Induced by inflammatory stimuli, IDO catabolizes tryptophan to kynurenine (KYN), which is subsequently converted into neuroactive metabolites. Here we summarize current knowledge concerning the relevance of the IDO pathway to CRF, including activation of the IDO pathway in cancer patients and, as a consequence, accumulation of neurotoxic KYN metabolites and depletion of serotonin in the brain. Because IDO inhibitors are already being evaluated as therapeutic agents in cancer, the elucidation of the relationship between IDO activation and CRF in cancer patients may lead to novel diagnostic and clinical approaches to managing CRF and its debilitating consequences., (© 2015 American Cancer Society.)

Objective: Several practice guidelines recommend routine screening for psychological distress in cancer care. The objective was to evaluate the effect of screening cancer patients for psychological distress by assessing the (1) effectiveness of interventions to reduce distress among patients identified as distressed; and (2) effects of screening for distress on distress outcomes., Methods: CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO, and SCOPUS databases were searched through April 6, 2011 with manual searches of 45 relevant journals, reference list review, citation tracking of included articles, and trial registry reviews through June 30, 2012. Articles in any language on cancer patients were included if they (1) compared treatment for patients with psychological distress to placebo or usual care in a randomized controlled trial (RCT); or (2) assessed the effect of screening on psychological distress in a RCT., Results: There were 14 eligible RCTs for treatment of distress, and 1 RCT on the effects of screening on patient distress. Pharmacological, psychotherapy and collaborative care interventions generally reduced distress with small to moderate effects. One study investigated effects of screening for distress on psychological outcomes, and it found no improvement., Conclusion: Treatment studies reported modest improvement in distress symptoms, but only a single eligible study was found on the effects of screening cancer patients for distress, and distress did not improve in screened patients versus those receiving usual care. Because of the lack of evidence of beneficial effects of screening cancer patients for distress, it is premature to recommend or mandate implementation of routine screening., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Addressing psychosocial needs, including key components of psychologic distress, physical symptoms, and health promotion, is vital to cancer follow-up care. Yet little is known about who provides psychosocial care. This study examined physician-reported practices regarding care of post-treatment cancer survivors. We sought to characterize physicians who reported broad involvement in (ie, across key components of care) and shared responsibility for psychosocial care., Methods: A nationally representative sample of medical oncologists (n = 1,130) and primary care physicians (PCPs; n = 1,021) were surveyed regarding follow-up care of breast and colon cancer survivors., Results: Approximately half of oncologists and PCPs (52%) reported broad involvement in psychosocial care. Oncologist and PCP confidence, beliefs about who is able to provide psychosocial support, and preferences for shared responsibility for care predicted broad involvement. However, oncologists' and PCPs' perceptions of who provides specific aspects of psychosocial care differed (P < .001); both groups saw themselves as the main providers. Oncologists' confidence, PCPs' beliefs about who is able to provide psychosocial support, and oncologist and PCP preference for models other than shared care were inversely associated with a shared approach to care., Conclusion: Findings that some providers are not broadly involved in psychosocial care and that oncologists and PCPs differ in their beliefs regarding who provides specific aspects of care underscore the need for better care coordination, informed by the respective skills and desires of physicians, to ensure needs are met. Interventions targeting physician confidence, beliefs about who is able to provide psychosocial support, and preferred models for survivorship care may improve psychosocial care delivery.

It has been more than 30 years since the first consensus development meeting was held to deal with guidelines of mammography screening. Although the National Cancer Institute has wisely focused on the science of screening and of screening benefits vs harm, many professional organizations, advocacy groups, and the media have maintained a focus on establishing who should be screened and promoting recommendations for which age groups should be screened. Guidelines have been developed not only for mammography but also for screening at virtually all major cancer sites, especially for prostate cancer, and most recently, with the preliminary results of the National Lung Screening Trial, for lung cancer. It seems clear that we have done an inadequate job of educating screening candidates about the harms and benefits of cancer screening, including the extent to which screening can reduce cancer mortality. We must also question whether our practice of summoning women to have mammograms, while providing men informed choice for prostate cancer screening, is consistent with a scientific analysis of the relative harms and benefits. We have spent a staggering amount of time and energy over the past several decades developing, discussing, and debating guidelines. Professional and advocacy groups have spent much time aggressively advocating the adoption of guidelines supported by their respective groups. It seems that it would be much more productive to devote such energy to educating screening candidates about the harms and benefits of screening and to engaging in shared decision making.

Background: Several practice guidelines recommend screening for depression in cancer care, but no systematic reviews have examined whether there is evidence that depression screening benefits cancer patients. The objective was to evaluate the potential benefits of depression screening in cancer patients by assessing the (1) accuracy of depression screening tools; (2) effectiveness of depression treatment; and (3) effect of depression screening, either alone or in the context of comprehensive depression care, on depression outcomes., Methods: Data sources were CINAHL, Cochrane, EMBASE, ISI, MEDLINE, PsycINFO and SCOPUS databases through January 24, 2011; manual journal searches; reference lists; citation tracking; trial registry reviews. Articles on cancer patients were included if they (1) compared a depression screening instrument to a valid criterion for major depressive disorder (MDD); (2) compared depression treatment with placebo or usual care in a randomized controlled trial (RCT); (3) assessed the effect of screening on depression outcomes in a RCT., Results: There were 19 studies of screening accuracy, 1 MDD treatment RCT, but no RCTs that investigated effects of screening on depression outcomes. Screening accuracy studies generally had small sample sizes (median = 17 depression cases) and used exploratory methods to set sample-specific cutoff scores that varied substantially across studies. A nurse-delivered intervention for MDD reduced depressive symptoms moderately (effect size = 0.37)., Conclusions: The one treatment study reviewed reported modest improvement in depressive symptoms, but no evidence was found on whether or not depression screening in cancer patients, either alone or in the context of optimal depression care, improves depression outcomes compared to usual care. Depression screening in cancer should be evaluated in a RCT in which all patients identified as depressed, either through screening or via physician recognition and referral in a control group, have access to comprehensive depression care.

National Institutes of Health consensus and state-of-the science statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; 3) questions and statements from conference attendees during open discussion periods that are part of the public session; and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the U.S. government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.

The call for interdisciplinary research in the war on cancer has escalated over the past several years. Behavioral science has played a key role in cancer control, and several exciting opportunities exist and will develop with the ongoing significant advances made in biomedical science. The current article briefly reviews the maturity of behavioral science in the areas of prevention, early detection, and survivorship and how the partnership of behavioral and biomedical science can effectively impact cancer incidence, morbidity, and mortality.

Cancer risk perceptions are a key predictor of risk-reduction practices, health behaviors, and processing of cancer information. Nevertheless, patients and the general public (as well as health care providers) exhibit a number of errors and biases in the way they think about risk, such that their risk perceptions and decisions deviate greatly from those prescribed by normative decision models and by experts in risk assessment. For example, people are more likely to engage in screening behaviors such as mammography when faced with loss-based messages than gain-framed messages, and they often ignore the base rate of a given disease when assessing their own risk of obtaining this disease. In this article, we review many of the psychological processes that underlie risk perception and discuss how these processes lead to such deviations. Among these processes are difficulties with use of numerical information (innumeracy), cognitive processes (eg, use of time-saving heuristics), motivational factors (eg, loss and regret aversion), and emotion. We conclude with suggestions for future research in the area, as well as implications for improving the elicitation and communication of personal cancer risk.

Despite numerous individual studies of psychological factors (depression, anxiety, distress) related to genetic testing for inherited cancer syndromes (CGT), there has been no systematic review of the psychological factors are measured among individuals at increased risk for hereditary breast, ovarian, or colon cancer. Our review provides an analysis of psychological factors in studies of CGT and discusses the instruments most commonly used to measure them. We performed a literature search using three major OVID databases from 1993 to January 2003. In the 19 studies that met our inclusion criteria, the most commonly assessed psychological factors were distress, anxiety, and depression. These factors were most often measured by the impact of event scale (IES), the state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies and Depression scale (CES-D), respectively. Our results show deficits in the existing body of literature on psychological factors associated with CGT including limited documentation of psychometrics and variability in instrumentation.

Background: Women with a first-degree relative with breast cancer are at increased risk of developing this disease. The optimal medical management of these women is unclear, with options including close breast cancer screening, bilateral prophylactic mastectomy, or participation in chemoprevention trials. Among women who undergo prophylactic bilateral mastectomy, very little is known about satisfaction with this surgery. Also, we know very little about variables related to prophylactic mastectomy decision making., Methods: Participants were women at increased risk of breast cancer due to family history. These women were categorized by self-report as not interested in prophylactic mastectomy (n = 58), interested but deciding against surgery (n = 92), or subsequently having a bilateral prophylactic mastectomy (n = 14). Information on screening practices, risk perception, level of depression, and cancer-related worry was collected. Women completing prophylactic mastectomy reported on their satisfaction with the surgery and breast reconstruction., Results: Women selecting surgery reported more breast cancer worry. The group expressing no interest in surgery reported fewer biopsies and lower risk estimates. Women completing surgery were satisfied with their decision, although satisfaction with reconstruction was mixed., Conclusion: Factors influencing surgical decision making may include breast-cancer-related worry, biopsy history, and subjective breast cancer risk.

Objectives: Bilateral prophylactic mastectomy is a drastic breast cancer preventive option for which indications are not standardized and efficacy has not been proven. To estimate the magnitude of this controversial practice, surgeons were surveyed on their recommendations about and performance of prophylactic mastectomy., Methods: A cross-sectional survey was sent to general surgeons (n = 522), plastic surgeons (n = 80), and gynecologists (n = 801) licensed to practice in Maryland in 1992. Proportions responding were 41.9%, 66.3%, and 54.9%, respectively. In addition, there were 30 respondents who identified "other" as their specialty. The respondents were asked about the role of bilateral prophylactic mastectomy and the number of times they had recommended and performed it in a year., Results: Seven hundred forty-two surgeons responded (51.8%). More plastic surgeons (84.6%) than general surgeons (47.0%) and gynecologists (38.3%) agreed that bilateral prophylactic mastectomy has a role in the care of high-risk women. Eighty-one percent of plastic surgeons had recommended the procedure, compared with 38.8% of general surgeons and 17.7% of gynecologists., Conclusions: Indications and practice patterns reveal heterogeneity of medical opinion and practice of prophylactic mastectomy. This study raises the need for better evaluation of the efficacy and appropriateness of prophylactic mastectomy.

At present, the care of women at increased risk of developing breast cancer poses a clinical dilemma and remains an area of controversy. A number of investigators have addressed the pros and cons of prophylactic mastectomy versus close follow-up, utilizing annual mammography, semiannual or even more frequent physical examinations of the breast, and proficient monthly breast self-examinations. Recent efforts to isolate a gene (BRCA1) on chromosome 17q12-21 raise additional concerns about the management of women testing positive for BRCA1 mutations. These women are estimated to have an 85% lifetime risk of developing breast cancer. Testing for BRCA1 mutation carriers may soon be available for population screening. This article describes preliminary studies investigating health care provider and patient perceptions of bilateral prophylactic mastectomy. In addition, a number of research questions remain regarding the efficacy and utilization of bilateral prophylactic mastectomy as a treatment option for women at increased risk of developing breast cancer. These women include those testing positive for BRCA1 mutations. In addition, women with a strong family history opting against testing for BRCA1 mutations may express interest in surgery.

While breast self-examination (BSE) frequency has received extensive research attention, proficiency has been less frequently addressed. Moreover, BSE proficiency among women at increased risk has not been adequately examined. Assessment of BSE proficiency is critical in determining the value of BSE with mammography and clinical breast examination in the early detection of breast cancer. BSE proficiency was assessed in 101 first-degree relatives of breast cancer patients. Participants were stratified by BSE frequency and randomized to one of two training techniques (MammaCare or concentric circle). BSE performance was assessed at baseline and at three follow-up visits at 4-month intervals. Proficiency was assessed by verbal description, a projected grid observational method, and lump detection ability on two breast models. BSE frequency was also assessed, in addition to BSE confidence, knowledge of breast cancer, risk perception, and worry related to breast cancer development. At baseline, proficiency was poor and correlations were not significant across assessment modalities. Significant improvement occurred on self-report measures, lump detection ability (true positives) on both models, and the projected grid. Improvement occurred across both training groups by the first follow-up, with no changes at subsequent visits. Both training techniques significantly improved BSE proficiency and were viewed positively by participants.

Little is known about breast cancer screening knowledge and behaviors among women with a family history of breast cancer. Data gathered from 125 first-degree relatives of breast cancer patients indicated that only 63.3% of women over age 35 "ever" had a mammogram, 53% of women 40 or older reported a mammogram in the last year, and only 36.8% of all participants reported monthly breast self-exam (BSE). Self-reported BSE competence was generally poor. One hundred five (105) (84%) reported a clinical breast exam over the previous year. Only 71 (56.8%) of the women indicated that they had been asked about their family history of breast cancer by their physician, and minimal information about risk related to family history was provided. Worry about developing breast cancer was positively related to mammography use and BSE competence. Confidence in performing BSE and learning BSE from a physician/nurse were both positively related to competence. Women who believed they had control over finding breast cancer in its early stages reported more frequent BSE. Poor compliance of women with a family history of breast cancer in the practice of BSE and utilization of mammography, and lack of risk information provided by physicians mandate a search for effective intervention.

Cancer risk analysis is a relatively new clinical service that has developed as more precise information has become available regarding specific risk factors. Both epidemiological and genetic factors contribute substantially to the identification of women at higher risk for developing breast cancer. The definition of what constitutes risk, an understanding of which factors influence risk, and the ability to present risk information clearly are critical features. In addition to providing information about risk and assessing each woman's perception of risk, the emotional issues must be addressed. The focus of intervention should center upon the benefits of early detection, assessment of breast self-examination skills, individualized breast cancer screening recommendations, such as mammography and physical exams, and recommendations for life style changes for possible prevention.

In preparation for studies of noradrenergic activity in anticipatory nausea and vomiting, we performed an open-dose study of clonidine to examine dose-toxicity relationships and indications of antiemetic activity. Nine patients, three each at 0.1, 0.2, and 0.4 mg/day, received clonidine twice a day for 5 days before chemotherapy. Unwanted effects, principally blood pressure reduction, dry mouth, and sedation, accumulated between 4 and 5 micrograms/kg/day. Four of eight evaluable patients had no anticipatory symptoms on clonidine. It is concluded that clonidine, at a dose of 4 micrograms/kg/day, might safely probe the role of noradrenergic activity in anticipatory nausea and vomiting.

The present study assessed the prevalence, severity, and other parameters of illness-related worry among 83 cancer patients receiving active treatment for their illness. Participants completed questionnaires assessing a variety of worry dimensions. In addition, a family member of each patient completed a brief questionnaire regarding their perception of the patient's illness-related worry. Nurse ratings of patients' clinic-related behaviors were obtained. Fifty-one percent (n = 43) of patients reported worry to be at least "somewhat of a problem." Fifteen percent (n = 12) reported it to be a significant to severe problem. Significant correlations included patients self-rating of worry and: nurse rating of clinic behavior, total score on a Worry Content Scale, ability to stop worrying once started, and impact of worry on mood and functioning. Rating by the significant other of how much of a problem worry was for the patient and whether the patient was a worrier preillness was also significantly correlated. There were no significant differences between "worriers" and "nonworriers" on demographic or disease variables. A logistic regression model using the categories of "worries" or "nonworriers" as a dependent variable found that women and patients reporting poor social support were more likely to report a problem with worry. However, a large amount of the variance remained unexplained.

A study performed 5 years ago in our clinic revealed a prevalence rate of 31% for anticipatory symptoms. This finding is consistent with other investigations. It was hypothesized that more effective management of postchemotherapy nausea and vomiting and briefer chemotherapy regimens since the previous study would decrease the prevalence of anticipatory symptoms. The study reported in this article assessed the prevalence of anticipatory symptoms in 121 patients receiving parenteral chemotherapy over a 7-week period. The overall prevalence rate of 33% for anticipatory symptoms was not significantly different from the previous study or other investigations. Length of postchemotherapy nausea was significantly related to the report of anticipatory symptoms. However, the severity of symptoms reported in the investigation was mild. The prevalence in patients on adjuvant therapy for breast cancer was also significantly reduced from the previous investigation. It is concluded that although anticipatory symptoms commonly occur they are only rarely clinically significant.

Two sessions of relaxation instructions were administered under high and low expectancy conditions. Fifty-four college students scoring high on a self-report measure of anxiety served as subjects. Live and taped abbreviated progressive muscle relaxation instructions and a self-relaxation condition were equally effective in reducing within-session self-report and physiological indices of anxiety. High expectancy instructions led to greater reductions in heart rate than did low expectancy instructions. Factors controlling anxiety reduction during relaxation therapies are discussed.