Complementary and Alternative Approaches to Cancer Prevention

Complementary and alternative medicine (CAM) includes a variety of therapeu- tic approaches not typically taught in conventional medical schools or used by the majority of conventionally trained physicians (Gordon and Curtin 2000).

Complementary refers to modalities used to complement, that is, used in addi- tion to conventional medicine, while alternative is usually used to describe treatments intended to replace conventional treatment (Murphy, Morris et al.

1997). Some such practices enjoy a history of research to support claims of effi- cacy but have not gained popularity among the majority of medical practi- tioners (e.g., use of acupuncture to reduce chemotherapy-induced nausea) (Dibble, Chapman et al. 2000; Mayer 2000; Shen, Wenger et al. 2000); others either lack or have unsupporting research to back claims of safety or efficacy (e.g., use of milk thistle to protect liver function during chemotherapy) (Ladas and Kelly 2003). Even so, the labeling of which modalities are complementary or alternative may shift over time as research and practice move some into conventional use and disprove others. Some practices less amenable to our current research epistemology may never move out of CAM nomenclature or perceptions (such as multi-modality system approaches, and perhaps, spiritual- ity).

Currently, CAM broadly encompasses a range of substances, practices, prac- titioners, and belief systems that fall outside of the conventional medical mod- el. CAM substances include botanicals (also known as herbs), vitamins, miner- als, specific nutrients, enzymes, foods, and homeopathy. CAM practices include yoga, Qigong, meditation, dietary modifications such as macrobiotic or raw food, and numerous culturally-based interventions focusing on various combi- nations of body, mind or spiritual interventions. CAM practitioners use thera- peutics with varying level of training, with great variation in licensing laws and insurance reimbursement depending on state (United States), province (Cana- da) or country (Cherkin, Deyo et al. 2002; Eisenberg, Cohen et al. 2002). These practitioners include, but are not limited to, naturopathic physicians, chiroprac- tors, acupuncturists, herbalists (both Western and Chinese), massage therapists, Ayurvedic practitioners, Native American healers, Tibetan physicians, Reiki prac- titioners, Healing Touch practitioners, and spiritual healers. Although conven- tional in many cultures, belief systems or perceptions of health, healing and the body that are considered to be CAM by conventional medical practitioners in the United States (U.S.) include Traditional Chinese Medicine (TCM), Ayurve- dic medicine, Tibetan medicine, and Native American medicine. These sub- stances, practitioners, practices, and belief systems have undergone varying

to Cancer Prevention

Linda K. Larkey

, Heather Greenlee

, and Lewis E. Mehl-Madrona

1

College of Medicine, University of Arizona, Tucson, AZ 85724

2

Mailman School of Public Health, Columbia University, New York, NY 10032

levels of scientific scrutiny, with the current emphasis in US research focusing on elucidating their biological mechanisms of action.

This chapter first addresses a variety of CAM modalities related to food, spices and botanicals. The research on these modalities most resembles con- ventional research on mechanisms of action, such as chemoprevention or diet- ary interventions that effect biochemical changes. This chapter also includes topics that are less well matched to the medical model of biochemical re- sponses, including: (a) approaches based on the mind-body relationship; (b) traditional systems of healing founded in ancient wisdom and practice; and (c) the more esoteric areas of spirituality and energy medicine.

CAM and Cancer Prevention Research

Although there are no proven methods to definitively prevent cancer in either conven- tional medicine or complementary and alternative medicine (CAM), many of the can- cer prevention approaches under investigation focus on dietary changes, nutritional supplements, lifestyle modifications (e.g., exercise), and decreasing environmental ex- posures, much of which falls into the field of CAM research.

Although the field of research on CAM in treatment of diseases, including cancer, has exploded in the past few years, there is a notable lag in the development of re- search protocols in the area of cancer prevention. Research on treating disease gener- ally progresses through systematic phases of theory development, lab and animal test- ing, then small pilot trials to large population studies. However, prevention research may follow a less convenient trajectory. Theories of cancer prevention often originate from correlational, longitudinal databases or observations of populations, national or cultural patterns of diet or lifestyle that might impact cancer rates (Krishnaswamy 1996). Following epidemiologic investigation, potential mechanisms for affecting the precursors or biomarkers of cancer development (and those associated with preven- tion of recurrence when applicable) are studied. Trials to investigate the effects of ac- tually manipulating such variables and eventually measuring cancer outcomes in CAM have yet to take a prominent role in the U.S. We are only just beginning to see the re- sults of large-scale national trials in conventional chemoprevention (e.g., BCPT, The Breast Cancer Prevention Trial) (Fisher, Costantino et al. 1998) and in nutritional in- terventions (CARET, Carotene and Retinol Efficacy Trial) (Omenn, Goodman et al.

1996). It will require funding opportunities for preliminary research to investigate CAM to demonstrate its effects on biomarkers before such large investments will be made for research in CAM in cancer prevention in the U.S.

Cancer patients and survivors have increasingly turned to CAM approaches for treatment and alleviating side-effects of treatment, making it more important for re- searchers to test safety and effectiveness of these alternatives (Bernstein and Grasso 1983; Cassileth and Deng 2004). Since CAM approaches are typically less targeted to- wards killing cancer cells and more focused on supporting the immune system and strengthen the capacity for self-healing (Gordon and Curtin 2000), such treatment modalities may also serve at-risk or healthy populations for prevention purposes.

The use of CAM in cancer prevention has not been thoroughly evaluated despite

growing evidence that the public is utilizing a wide range of practices and products with

that intent. In 1990 it was estimated that 425 million visits to CAM providers were made

in the U.S. (as compared to 388 million visits to conventional caregivers), and that CAM expenditures for that year in the U.S. amounted to approximately $13.7 billion (Eisen- berg, Kessler et al. 1993). Estimates for out-of-pocket expenses rose to $27 to 34 billion by 1997 with a ªstaggering 629 million visits to alternative practitionersº (Neal 2001).

Specific to cancer prevention, a recent study showed that 55% of sampled men with a family member diagnosed with prostate cancer were using some form of CAM and 30% were using supplements specifically purported to be prostate-specific cancer pre- vention agents (Beebe-Dimmer, Wood et al. 2004).

Foods, Spices, and Herbs

CAM cancer prevention strategies that employ foods, spices, botanicals, and specific nutrients are directed towards specific physiological pathways. Certain agents have a number of possible chemopreventive effects including antioxidant, immune modulat- ing, hormone modulating, anti-angiogenic, apoptotic, and anti-metastatic properties.

These have been described elsewhere (Boik 2001; Park and Pezzuto 2002). Some of the most promising candidates for further exploration, according to the existing literature, are summarized here.

The definitive line between a food, a spice and a botanical is easily blurred depend- ing on how substances are prepared or formulated. For example, garlic may be consid- ered a food, a flavoring, or extracted for botanical supplementation. In general, a food is considered something that is eaten as a primary source of nutrition. Much of the food chemoprevention literature focuses on fruits, vegetables and whole foods (i.e.

foods that have not been commercially processed) (Vainio and Bianchini 2003). Cruci- ferous vegetables, fiber and soy are currently under investigation for activity in cancer prevention. These are addressed in this book's chapter on ªBody Composition, Diet and Physical Activity.º Other research efforts in cancer prevention are focused on the benefits of a specific diet, such as a macrobiotic diet (Kushi, Cunningham et al. 2001).

Spices are the aromatic parts of plants that are used as seasonings, rather than for nutrition. Some spices, as well as many foods, contain concentrated amounts of phyto- chemicals (naturally occurring biochemicals that give plants their color, flavor, smell, and texture) that may have preventive properties (Polk 1996; Nishino, Tokuda et al.

2000). Many of these properties have been demonstrated in in vitro and animal stud- ies, with only limited data in humans (Lampe 2003). Antioxidants, which help prevent free radical formation and damage, are found in cloves, cinnamon, oregano, pepper, ginger, garlic, curcumin, coriander, and cardamom (Wu 2004). Biotransformation en- zymes, which metabolize chemical carcinogens, are induced by coriander, curcumin, cinnamon, and Wasabia japonica (Japanese domestic horseradish). Garlic, cloves, cin- namon, chili, horseradish, cumin, tamarind, black cumin, pomegranate seeds, nutmeg, onion, and, celery have all demonstrated antibacterial activity. Ginger and curcumin have anti-inflammatory properties.

Botanicals, more commonly known as herbs, may be fresh, dried, freeze-dried,

juiced, or extracted. Either the whole or specific parts of the plant are used, including

the leaf, flower, stem or root. Much of the cancer-related research on botanicals to

date focuses on the role of botanicals to treat cancer (e.g., mistletoe extract) (Zarkovic,

Vukovic et al. 2001). However, most research in botanical chemoprevention has been

limited to work in vitro (cell lines) and in vivo (biomarker evaluation).

The specific agents reviewed below provide examples of the various mechanisms being investigated in botanical chemoprevention research: curcumin for its antioxidant and anti-inflammatory properties; flaxseed for its hormone modulating effects; mush- rooms for their immune modulating properties; and ginseng for its immune modulating and adaptogenic effects. It is imporant to note that these and other herbal agents have active substances that may interact with other herbs, supplements or medicines and that may have unexpected side effects. Herbal products that modulate certain enzymes or proteins may have adverse interactions with anti-cancer medications (e.g., ginko, echina- cea, ginseng, St. Johns wort, kava) (Sparreboom, Cox et al. 2004). All foods, spices and herbs used for medicinal purposes should only be taken under the care and supervision of a practitioner highly trained in the area of botanical medicine.

Curcumin

Curcumin, an extract of tumeric, has attracted attention as a potent antioxidant with anti-inflammatory effects. It has demonstrated antitumorigenesis effects in experimen- tal mouse models (Miquel, Bernd et al. 2002; Youssef, El-Sherbeny et al. 2004). It has also shown protective effects against DNA damage in human peripheral blood lym- phocyte cells in both smokers and non-smokers. Recent studies of potential mecha- nisms of curcumin effects on invasive lung adenocarcinoma cells indicate that it may inhibit invasion via the regulation of selected gene expression (Chen, Yu et al. 2004).

In colon cancer cells, curcumin has demonstrated the ability to induce apoptosis in cells expressing Cox-2 (Agarwal, Swaroop et al. 2003). Curcumin is a promising agent with a similar mechanism of action as other agents currently being investigated in the prevention of colon (Xu 2002), breast (Shen and Brown 2003), skin (Bachelor and Bowden 2004) and other cancers (Grossman 2003).

Flaxseed

Flaxseed is rich in lignans (a type of phytoestrogen) and fiber. Lignans are proposed to have chemoprotective properties in breast cancer due to their inhibition of estrogen production; they have been shown to inhibit growth of human mammary tumor cells (Hirano, Fukuoka et al. 1990), reduce mammary tumor initiation (Thompson, Seidl et al. 1996), stimulate sex hormone binding globulin which binds estrogens that increase cancer risk (Adlercreutz, Mousavi et al. 1992), and inhibit aromatase activity which then decreases endogenous estrogen level (Adlercreutz, Mousavi et al. 1992; Adler- creutz, Fotsis et al. 1994). More recent studies have focused on how flaxseed influences endogenous hormone concentration and urinary estrogen metabolites associated with increased cancer risk. Flaxseed in the diet has been shown to significantly reduce se- rum concentration of 17-beta-estradiol and estrone sulfate (Hutchins, Martini et al.

2001). Flaxseed supplementation significantly increased urinary 2-hydroxyestrone ex- cretion and increased the 2:16 alpha-hydroxyestrone ratio in pre-menopausal (Hag- gans, Travelli et al. 2000) and post-menopausal women (Haggans, Hutchins et al.

1999). Flaxseed's influence on hormones (e.g., testosterone) and its high content of

omega-3 fatty acids has led to initial research on its potential role in the prevention of

prostate cancer (Demark-Wahnefried, Price et al. 2001).

Immune modulating mushrooms

Several mushrooms have been identified as having potential immune modulating ef- fects (Pelley and Strickland 2000). Coriolus versicolor, historically used in Traditional Chinese Medicne (TCM), is often used in extract form. A protein-bound polysaccha- ride-K (PSK) and polysaccharide-P (PSP) from the mushroom is currently under in- vestigation as a preventive and as an anti-cancer agent. Recent research has shown immune-stimulatory actions of these polysaccharides on T lymphocytes, B lympho- cytes, monocytes/macrophages, bone marrow cells, natural killer cells, and lympho- cyte-activated killer cells as well as promoting the proliferation and/or production of antibodies and various cytokines such as interleukin (IL)-2 and IL-6, interferons, and tumor necrotic factor (Chu, Ho et al. 2002; Fisher and Yang 2002). Maitake mushroom (Grifola frondosa) is an edible mushroom that is also under investigation for its anti- cancer properties. The most active ingredients in this mushroom appear to be poly- saccharides 1,3 and 1,6 beta-glucan). These constituents are marketed in the form of proprietary D- or MD-fraction extracts. Maitake extracts have been shown to enhance bone marrow colony formation in vitro (Lin, She et al. 2004), induce apoptosis in prostate cancer cells (Fullerton, Samadi et al. 2000), and activate NK cells in cancer patients (Kodama, Komuta et al. 2003).

Ginseng

Several botanicals are purported to have adaptogenic effects that provide resistance to stress and fatigue. The most active components of Panax ginseng (Asian ginseng) are ginsenoside saponins (Tyler 1993). There are approximately 30 different saponins that have been isolated from Panax ginseng; a number of these have been evaluated for their potential use in the field of cancer prevention (e.g., ginsenoside Rg

, Rg

, Rh

, and Rh

) (Yun, Lee et al. 2001). The quantity of ginsenoside in roots vary by type and age of the plant. Ginsenosides have been shown to stimulate the immune system and inhibit cancer cell proliferation (Xiaoguang, Hongyan et al. 1998). Preliminary in vitro and epidemiologic evidence show non-specific preventive effects in multiple tumor sites (Shin, Kim et al. 2000; Yun 2001; Yun, Choi et al. 2001; Yun, Lee et al. 2001;

Chang, Seo et al. 2003; Yun 2003).

While these and other botanicals show promise for a number of biological mecha- nisms related to cancer prevention, randomized controlled trials are needed in hu- mans before they can be advocated as effective chemoprevention agents.

The Mind-BodyConnection

Mind-body approaches to health are those practices that generate states of mental and physical relaxation (e.g., meditation), or those that strive to improve attitudes and emotions regarding health (e.g., psychotherapy and support groups). A long history of research has explicated numerous ways in which psychology interacts with physiology.

Much of this work has been in the area of stress. The mechanisms of stress, and stress

reduction through mind-body techniques, have been thoroughly described through

more than five decades of research. Early work on stress and health focused on the

correlates of risk and incidence of heart disease (Friedman and Rosenman 1974). In

the 1980s, the emerging field of psychoneuroimmunology demonstrated the relation- ship between the hypothalamus, psychological states and immune function. This work began to extend the paradigm of the stress response to incorporate much more so- phisticated models of the interactions between mind and body (Ader, Felten et al.

1991; Pert 1997; Zorrilla, Luborsky et al. 2001).

Much of the CAM literature written for cancer patients provides thorough reviews of mind-body options to consider and suggests the potential use of mind-body tech- niques for prevention of recurrence of disease (Lerner 1994; Gordon and Curtin 2000). Theories and research exploring the relationship between immune, nervous, and endocrine systems relate these factors directly to the development and progres- sion of cancer. Current theories and ongoing research are contributing to our under- standing of the effects of analogues of hypothalamic hormones on hormone-depen- dent cancer, the role of opioids and melatonin on cytokines, gene modulation, and the immune responses to psychotherapy in cancer patients (Temoshok 1987; Holland 1989; Schipper, Goh et al. 1995; Conti 2000; Elenkov and Chrousos 2002).

Stress and Immunity

Stress has a central role in health and well-being; the cascading effects of stress are known to have numerous consequences. Initially affecting the sympathetic nervous system with concomitant releases of epinephrine and norepinephrine, stress raises blood pressure and heart rate as a coping response. Activation of the hypothalamic-pituitary-adrenal (HPA) axis mediates the body's response to stress, exerting effects on the various periph- eral target tissues through glucocorticoids. The acute stress response is associated with beneficial effects that help the individual survive a challenge by mobilizing fuels for en- ergy, inhibiting reproductive behavior and increasing arousal and vigilance. However, when the body is chronically challenged, whether it is continuous or in intervals that are too frequent to allow for recovery and/or adaptation, these effects are detrimental and lead to an increased risk of disease (Raison and Miller 2001). Dysregulation of the sympathetic nervous system/HPA axis (due to increased exposure to cortisol), is hy- pothesized to contribute to the physiological decrements that accompany diseases asso- ciated with aging and suppressed immune function, factors implicated in cancer risk.

Interventions that use combinations of meditation, breathing, and movement indicate that responses to stress may be attenuated through such practice. Mind-body methods then emphasize breathing along with progressive muscle relaxation, meditation, yoga postures, or autogenic training (a technique that uses a combination of attention and so- matic suggestion to assist relaxation) have been shown to help in reduction of hyperten- sion (Astin, Shapiro et al. 2003), increased phagocytic activity (Peavey, Lawlis et al. 1985) and lowering of cortisol levels (Schmidt, Wijga et al. 1997; Kamei, Toriumi et al. 2000;

Gaab, Blattler et al. 2003). Mindfulness meditation has become one of the more standard-

ized and popular methods of meditation taught in the West. Studies show direct im-

provements of immune function among other health indicators in response to this form

of meditation, which focuses on breathing, relaxation and a full consciousness of one's

surroundings (Kabat-Zinn 1994; Williams, Kolar et al. 2001; Davidson, Kabat-Zinn et

al. 2003). Popular among cancer patients since the late 1970s are the visualization tech-

niques promoted by Carl Simonton (Simonton, Simonton et al. 1978). Preliminary stud-

ies of this technique have shown improvements in leucocyte and natural killer cell activ-

ity in response to imagery of healthy immune systems and retreating cancer cells (Ach- terberg and Lawlis 1984; Kiecolt-Glaser, Glaser et al. 1985; Gruber, Hall et al. 1988).

Qigong and tai chi exercises, ancient TCM practices that include breathing and movement, are often seen as mind-body approaches to health. Tai chi is one of the forms of qigong exercise that has become increasingly popular in the U.S.; qigong is gaining in use and popularity. The effects of qigong and tai chi are theoretically linked to the reduction of stress (Kerr 2002). These practices hold potential for affecting the immune system; there are reports of increased phagocytic activity, lymphocyte trans- formation, and improved cytokine profiles among those who practice qigong (Liu, Xu, Guomin et al. 1988; Chen and Yeung 2002) and similar results have been shown for tai chi practice (Wang, Collet and Lau 2004). One of the few studies of Qigong exer- cise effects on immunological function published in the U.S. showed a reduction in cortisol and an increase in the number of the cytokine-secreting cells (in particular, significant increases in the IFNgamma:IL10 ratio) (Jones 2001). Although much of the research on the mind-body connection has been done in the context of cancer pa- tients, immune system responses may arguably translate to cancer prevention for those who utilize mind-body techniques in the context of wellness (Engelking 1994).

Psychological States, Interventions, and Cancer

Although theories have been proposed to associate certain predispositions of personal- ity or psychological factors with the development of cancer, the research has been in- consistent making it difficult to summarize conclusions (Garssen and Goodkin 1999).

Prospective studies have implicated a number of possible psychological risk factors for developing cancer, with the most consistent finding being repression of emotion or depression (Dattore, Shontz et al. 1980; Temoshok, Heller et al. 1985; Hislop, Waxler et al. 1987; Temoshok 1987; Kaasa, Mastekaasa et al. 1989) yet even these have been dis- puted (Hahn and Petitti 1988; Kreitler, Chaitchik et al. 1993). Preliminary understand- ing of these issues might best be studied in the context of survival, in that the factors influencing survival time may represent similar mechanisms that prevent recurrence.

Work with animal models has clearly shown a relationship between psychological de-

terminants and tumor growth (LaBarba 1970; Sklar and Anisman 1981; Visintainer, Se-

ligman et al. 1983), but in the human arena the relationship between psychology and the

course of cancer progression is less clear. Factors shown to improve outcomes include

social support (Ell, Nishimoto et al. 1989; Waxler-Morrison, Hislop et al. 1991), greater

expression of distress, smaller numbers of severe or difficult life events (Ramirez, Craig

et al. 1989), and ªfighting spiritº (Pettingale, Morris et al. 1985). A discussion of the po-

tential role of psychological variables moved to the forefront in 1989 with the publication

of research that found a positive effect of a psychosocial intervention on breast cancer

patients' survival time (a study that has since been called into question due to differences

in baseline characteristics of patients and other study design issues) (Spiegel, Bloom et

al. 1989). This study kicked off a series of similar research projects, but all trials specif-

ically designed to test the impact of a psychological intervention on survival have so far

given inconclusive results. Nevertheless, clinical experience points to the existence of a

minority of cancer patients who make strong efforts to help themselves psychologically

and appear to live longer than expected (Ikemi, Nakagawa et al. 1975; Achterberg, Math-

ews-Simonton et al. 1977; Roud 1986; Berland 1995).

Cunningham (Cunningham, Phillips et al. 2000; Cunningham, Phillips et al. 2002) conducted an exploratory study on metastatic cancer patients enrolled in a year-long psychospiritual intervention. Standard psychometric instruments did not predict length of survival in this study, but a subsequent analysis of qualitative interview data from 22 participants suggested that there may be a survival benefit among those who (a) believed that the group activity would help them, (b) invested a greater level of effort in the group activities, (c) engaged to a greater degree in personal and spiritual change, and (d) had improved perceptions of quality of life as compared to those who did not.

This finding may help explain the inconclusive results of previous studies that have randomized patients to intervention or control groups; those predisposed to involve themselves in psychological work may find opportunities in the context of an inter- vention or may seek such opportunities on their own. Furthermore, if only a small proportion of the patients in a therapy group become strongly involved in trying to help themselves psychologically, and theirs are the only lives substantially prolonged, this effect may be ªdiluted outº when group means are calculated. A randomized, con- trolled trial would thus need to be exceedingly large to produce a reliable treatment effect and would likely need to control for patients' expectations.

Given Cunningham's findings, there is reason to suspect that, although more chal- lenging to design than originally thought, there is great potential for finding more ro- bust relationships between the psychological, social, and even spiritual factors asso- ciated with patient involvement in their own healing. Preventing a recurrence of can- cer may similarly be dependent upon a set of psychoneuroimmunological factors.

Although developing a sense of purpose in life, having a supportive community, and having faith for healing may not manifest in the same way with healthy individuals as with those who have been challenged by a diagnosis of cancer, these factors are worth examining as reducing risk for disease as well as improving patient quality of life.

Social support and spirituality have been shown to be related to longevity and gen- eral health. Improved outcomes have been demonstrated in some studies of cancer pa- tients who have strong social support (Worden and Weisman 1975; Funch and Mar- shall 1983); other studies have found no survival benefit (Goodwin, Leszcz et al.

2001). Investigations of the relationships between spirituality and cancer is based on the evidence that overall improved health has been shown to be related to spirituality, and healthy behaviors have been correlated with religious practice (Schiller and Levin 1988; Levin and Vanderpool 1991; Daaleman, Perera et al. 2004; Daniels, Merrill et al.

2004; Reindl Benjamins and Brown 2004). Continuing to explore social, psychological, and spiritual factors related to the mind-body connection may prove fruitful, but there remains a need for evidence regarding the specific mechanisms of these mind-body approaches that affect cancer outcomes.

Wellness

Much of the interest in CAM from the public and practitioners has been guided by

and intrinsically linked to emerging views based on the concept of ªwellness.º The

wellness concept became popular in the early 1970s, and out of that original thrust,

many wellness centers began to emerge, some with a cancer focus, most without a

particular disease focus. The term ªwellnessº has come to denote a way of thinking

about health that goes beyond the simple absence of disease. In theory, wellness is not

necessarily sought from a position of avoiding disease, but is holistic in the sense that it seeks to achieve greater balance and awareness in body, mind, and spirit, an evolu- tion of one's whole being (Benson and Stuart 1993).

Several of the culturally-based systems of health, such as Traditional Chinese Medi- cine (TCM), Ayurvedic medicine, and practices associated with Native American heal- ing, match the holistic precepts of wellness. Although there may be practitioners and patients with a single-minded focus on a particular modality, most proponents of CAM view health as multifaceted, promoting balance and wellness of body, mind, and spirit. Because the systems promoting wellness tend to be broad in focus, prevention of a specific disease such as cancer is not an exclusive goal. Nevertheless, the expected outcomes of improved wellness include enhanced immune function, stamina and over- all well-being, factors that may reduce the risk of cancer as well as other diseases.

There is a particular challenge for drawing conclusions about the cancer preventive potential of wellness-focused systems. Most are promoted as an entire wellness pack- age, where a set of principles guide lifestyle, such as diet, form of exercise, meditation or other mindful practices, spiritual views, and even botanicals, specifically chosen for balance based on the philosophy of that system. In the context of cancer treatment, several of these systems propose paradigms of etiology and progression, as well as healing, that are very different from the Western medical model, which focuses on the treatment of a specific diagnosis or symptom.

Researching non-Western systems is problematic. The multiple modalities usually prescribed for treatment are based on individual readings of the various levels of in- volvement in body, mind, social, environmental, and spiritual factors. Research meth- ods are not designed to test non-Western systems that treat every individual differ- ently according to particular needs. Because of the lack of accepted research method- ology that is able to test this holistic approach to health, it is important that health care practitioners become aware of, and researchers to begin to solve the puzzles of, scientifically understanding these integrated systems.

CAM practitioners promote balance for healing or for overall well-being, but the goals of achieving wellness are put into the hands of the individual taking responsibil- ity for her or his own health (Wong and McKeen 2001). The movement toward self-re- sponsibility in health and examining life as a whole are principles that sprouted in Western culture. This movement took place concurrently with a rekindled interest in more natural forms of healing that included mind-body approaches, spirituality, and non-Western medical practices, and has been especially powerful among cancer pa- tients (Tatsumura, Maskarinec et al. 2003).

An exemplar of this philosophy is the Wellness Community, an international net- work of non-profit centers ªdedicated to providing free emotional support, education and hope for people with cancer and their loved onesº (Benjamin 1995; Penson, Talsa- nia et al. 2004). Using a whole-person (holistic) approach, patients are encouraged to actively support each other ªto regain control, reduce feelings of isolation and restore hope-regardless of the stage of diseaseº (Penson, Talsania et al. 2004). Varieties of meditation, Qigong, massage, yoga, Reiki, healing touch, and other such practices are common in these centers, which make available to cancer patients a supportive com- munity as well as opportunities for spiritual, emotional and physical healing.

Popular writers such as Dr. Bernie Seigel (Seigel 1990) and Dr. Andrew Weil (Weil

1995) have intrigued the minds of readers with stories of healing as well as stories of

profoundly changed lives. Many of these stories are recounted in books that catch the attention of the public, inspiring faith in the human ability to get well and stay well.

For example, Dr. Caroline Myss, in her book about power and healing, suggests ex- ploring symbolic meaning and balance, taking the reader through religious symbols, archetypal challenges, and stage-of-life passages to address life lessons and points of transition (Myss 1996). Moving through these lessons with conscious response is theo- rized to bring spiritual health cascading down through the psychological and physical systems. Even though Dr. Myss describes case histories of patients with cancer or pre- cancerous conditions who get well, there is not sufficient documentation of measur- able physiological outcomes over time, nor comparison to matched cases, to draw conclusions.

Research on spontaneous remission was more prevalent in the early 1900s; numer- ous examples defy our current understanding of the disease process (O'Regan and Hirshberg 1993). A common ingredient in these healing testimonies is spirituality (Hammerschlag 1988; Struve 2002). It is important for the reader to understand that these are testimonies, not scientific research. The role of spirituality in wellness, although only emerging in western societies over the past few decades, might be seen as a reclamation of ways of viewing health and life that have been prevalent in most cultures and societies worldwide.

Indigenous Cultural Systems of Healing

Many cultures throughout the world have produced comprehensive, sophisticated sys- tems of describing disease states and methods of healing that are very different from the Western medical model. What characterizes many of the systems, and distin- guishes them from western medicine, is the tendency to consider health to be a sys- tem of balance among body, mind and spirit-often including social and environmental factors as part of the whole in some systems, rather than a constellation of biochem- ical and hormonal balances identified at a microbiological level. From African healing arts to Samoan fofo; from Native American ceremony to Traditional Chinese Medicine, it appears that nearly all of the indigenous cultural systems view human health in the context of the natural world around us as well as the interaction of physical elements with mind and spirit (Kaptchuk 1983; Mehl-Madrona 2003; Mishra, Hess et al. 2003).

Each of these systems of healing typically has theories of how particular diseases develop, and consequently suggest tactics for prevention. Health and disease is under- stood in the context of a particular person's experience of life, family, dietary and en- vironmental factors, social conditions, and spiritual responses. Ayurvedic medicine and Native American healing are given as two examples of systems of healing that promote living in harmony with nature, with one's given constitution, and connecting to spirit as ways to stay healthy.

Ayurveda

In Ayurvedic medicine, the build-up of toxic residues termed ªamaº (more than physi-

cal substances in biomedical terms, but more subtle essences produced by imbalances

in living, diet, and mental/emotional states) is believed to be one of the main causes

of cancer. Recognizing one's primary ªdoshas,º or essential natures, and living a life-

style to manage and balance these elements alongside cleansing techniques designed to rid the body of ama, are considered to be the best approach to avoiding cancer from the Ayurvedic point of view (Chopra 2000; Herron and Fagan 2002). Ayurvedic medicine uses the terms ªmindº and ªconsciousnessº to refer to the origin of physical conditions. ªWhen you look at Ayurveda's anatomical charts, you don't see the familiar organs pictured in Gray's Anatomy, but a hidden diagram of where the mind is flow- ing as it creates the body. This flow is what Ayurveda treatsº (Chopra 1989).

Although the combination of these many lifestyle and mind-body approaches are seen as central to treating cancer, one agent Maharishi-4, an Ayurvedic food supple- ment, has been shown to regress mammary tumors in rats and has been evaluated for other anti-cancer effects due to its potent anti-oxidant properties (Fields 1990; Shar- ma, Dwivedi et al. 1990). Given that this is only one of the many modalities used in Ayurvedic medicine, and more emphasis is placed on building balance through assess- ment and lifestyle changes to support essential constitutions, much work must be done to test the potential for this system to affect cancer risk. Singh (Singh 2002).

provides a much needed framework for presenting various aspects of Ayurvedic prac- tice in cancer treatment, linking theoretical constructs of that system to potential ex- planations of medical biomarkers that could be explored to begin explicating mecha- nisms of action for treatment and prevention.

Deepak Chopra, M.D., has done much to promote the concept of mind-body heal- ing and wellness through his center and his book entitled Perfect Health; The Complete Mind-Body Guide. This book repackaged Ayurvedic principles of healing into an approach more palatable to Western tastes. The details of the Ayurvedic system are generalized to principles that are recognizable in modern wellness teaching (Chopra 2000). Such programs continue to represent the basic tenets of wellness±balance in life and responsiveness to life's lessons. These basic tenets are hypothesized to bring opti- mum health, and hence may also prevent cancer.

Native American Healing Traditions

With so many tribes indigenous to the Americas, each with unique healing traditions, it becomes impossible to define a particular tradition as representative of Native American healing. There are, however, some themes that are common throughout the Americas. For example, Native American healers generally do not conceptualize a medicine-religion differentiation. Healing must acknowledge an Inner Healer. Accord- ing to Dineh (Navajo) healer, Thomas Largewhiskers, this inner force explains why people get well or not, or how they stay healthy in the first place (Largewhiskers 2004). Many tribes and other indigenous cultures teach that spirit is indivisible from mind and body and that a healthy balance and connection with spirit is the path to prevention of disease.

An important source for connecting with spirit for healing and balance, for healthy and ill alike, is ceremony. Ceremony is not unique to Native American culture; it is often represented in one form or another in health systems that include a spiritual component (Hammerschlag and Silverman 1997). The importance of ceremony is consistent with the hypothesis that religiosity/spirituality may be associated with physiological processes ± including cardiovascular, neuroendocrine, and immune function (Seeman, Dubin et al.

2003). Immune function is important in cancer and its prevention. Although the evi-

dence has not demonstrated that spirituality slows the progression of cancer, studies con- ducted to date have been small and limited (Powell, Shahabi et al. 2003). In cultural sys- tems that involve ceremony, prevention should address mind, body, and spirit.

Native American healing practices often hinge upon the skills of the medicine man who is able to intervene for the patient in the spirit world, and can ªseeº or listen to messages provided by Spirit to help the patient, including how to change aspects of the person's individual spirit or energy body through sound, touch, or prayer. This is a traditional way of viewing what is now often called ªenergy medicine,º a field that combines technology, physics, and ancient wisdom for healing.

EnergyMedicine

Energy medicine is often used to refer to practices that involve subtle or very low in- tensity nonmaterial stimuli for purposes of healing (Rubik 1995). These stimuli may be artificially generated electromagnetic fields (e.g., Pulsed Electromagnetic Field Therapy) or healing energies emitted by humans (e.g., Reiki, Healing Touch), and are theorized to work by causing a change in the human biomagnetic energy field and subsequently in biochemical responses.

Energy medicine includes a wide range of therapies. As noted above, many of the in- digenous systems of healing acknowledge a life force such as Qi (the force that runs through meridians as defined in TCM), prana (in yoga practice and Ayruvedic medicine) or the fields of energy perceived and manipulated by those practicing any of the forms of energy healing (e.g., Healing Touch, Reiki, Therapeutic Touch). For purposes of this re- view, a broad definition will be used to encompass any modality designed to improve overall balance of the energy field either through internal intent or external application.

The mechanisms by which energy healing may work to improve health are still being ex- plicated. Without knowing yet whether there is one underlying principle or many ways in which nonmaterial stimuli might affect energy fields and, in turn, biological out- comes, these modalities will be considered as similar in this review.

The term ªbiomagnetic fieldº refers to the various electromagnetic fields that run through and around the body (Oschmann 2000). Electrical impulses generated in the heart and brain (as measured conventionally via electroencephalograph, or EEG, and electrocardiogram) are known to generate biomagnetic fields. Such fields have been detected by trained energy medicine practitioners as emanating from the whole body as well as specific parts, notably the hands.

The most controversial aspect of energy medicine is the assumption that biomag- netic fields are more than artifacts of electrical activity in the body and that they not only provide indicators of health, but that they can be altered to produce improved states of health. For example, TCM is based on the concept that there are flows of en- ergy that can be mapped representationally across the surface of the skin (although they are believed to flow through and beyond the limits of the physical body). These flows have names that link them to organs of the body (e.g., liver meridian or kidney flow), but their function is seen as much broader, including emotional and symbolic as well as physiological functions.

Applications of electromagnetic fields within certain frequency ranges have been

shown to have a number of biological consequences with potential application in med-

icine. Pain control using transcutaneous electrical nerve stimulation (TENS) is one of

the more well-known developments in energy medicine. Tissue regeneration, bone re- pair (Sharrard 1990), improvements in osteoarthritis (Trock, Bollet et al. 1993), soft tissue wound healing (Becker 1990; O'Connor, Bentall et al. 1990), neuroendocrine modulations, and immune system stimulation (Cadossi, Emilia et al. 1988; Cadossi, Iverson et al. 1988; Cossarizza, Monti et al. 1989) have all been documented in re- sponse to various forms of electromagnetic stimuli. The usefulness for such externally, artificially applied therapies for cancer prevention have not been demonstrated; re- sponse to such therapies has only been documented in the context of disease.

The purpose for addressing the emerging field of energy medicine in the context of cancer prevention is twofold: 1) to explicate the non-Western theories underlying en- ergy medicine approaches; and 2) to discuss the theory inherent in energy medicine- based systems that early correction of stagnation or imbalances in energy patterns may lead to the prevention of cancer. Non-Western theories are based on the concept that there are flows of energy or essence patterns in the body that are dynamically balanced and must not be blocked; the blockages of energy will allow the development of disease, including tumors and eventually cancer. Energy based medicine systems at- tempt to unblock these flows through various methods such as acupuncture treat- ments, specifically designed Qigong exercises, or externally applied biomagnetic emis- sions from the hands of a healer. Even more remarkable is the hypothesis that detec- tion of neoplastic changes may be possible with methods that assess Qi imbalance.

One of the oldest documented forms of energy healing is the practice of qigong.

An area of practice foreign to western medicine and philosophy, qigong is typically considered to be comprised of two forms, external and internal qigong. External qi- gong or external qi healing (ªwai qiº or ªwei qiº) (Cohen 1997; Johnson 2000), an an- cient Chinese method of healing touch, refers to the emission or direction of qi, theo- retically similar to healing touch methods described above. It is administered by transfer from the hands of experienced qigong practitioners to other individuals for the purposes of healing or improving health. Trials of healer interventions have dem- onstrated a variety of healing effects on the human body (Benor 1993; Schwartz, Swa- nick et al. 2004).

The potential for Qigong exercises (i.e., internal qigong) designed to balance the meridians to have an effect on health indicators such as cytokine profiles has already been discussed in the section on mind-body interventions. Emitted qi also has been shown in numerous studies to have immune modulating effects, mostly reported from research conducted in China with incomplete information on study design (Liu). Pre- liminary evidence is good for demonstrating potential of qi emission to strengthen cellular immune function in animal models and humans.

More notable are the results that are beginning to be published in the U.S. on ef- fects of qi emission (external qigong) on growth of induced lymphoma in mice.

Although results seemed inconclusive relative to varying abilities of practitioners, one of the studies showed significant differences in tumor inhibition between intervention and control mice (Chen, Shiflett et al. 2002).

Beyond these claims, most of which focus either on healing for specific conditions,

or improvement in immune status, there is much to be learned from the theories and

practice of qigong. In this paradigm of health, the goal of balancing qi is woven

through the practices. From the qi emission from the hands of a master practitioner

who ªseesº the blockages and areas of need in the biofield, to the exercises designed

for movement of qi through specific meridians, to the herbal remedies that stimulate, calm or unblock meridian flow, each modality is intended to move one toward greater health. Validating through research a system so focused on prevention of disease, catching the imbalances in the energy field before illness manifests, seems unlikely.

Many people are familiar with the idea that TCM includes a range of modalities, such as acupuncture and herbal remedies. What is less well-understood is that these treatments are all designed to influence the energy map of the body; in TCM, a net- work of energy lines called meridians represent various organs and functions, physical and emotional, and the balance of these are purported to maintain health. The theory behind a particular remedy is not necessarily direct action upon an organ or a bio- chemical reaction (as is the case with Western views of herbs), but rather its effects on promoting, inhibiting, or balancing the targeted energy meridians (Kaptchuk 2002).

Explanations for what structures in the body might account for positional relation- ships to energy phenomena have more recently been proposed, most notably in the context of acupuncture. The clinical efficacy of acupuncture has been demonstrated in numerous studies, yet the theories of how it functions according to TCM are often not accepted even by physicians who practice this form of energy medicine (Kaptchuk 2002). Neurohumoral approaches in acupuncture research were instrumental in estab- lishing the scientific validity of acupuncture. Recent advances in the morphogenetic singularity theory suggest that acupuncture points originate from the organizing cen- ters in morphogenesis. Possible mechanisms of action are not necessarily dependent upon an association with nervous or lymphatic systems; acupuncture points and meri- dians have been shown to have high electric conductance that is related to high den- sity of gap junctions in cellular structure (Shang 1993; Shang 2001).

There is evidence that acupuncture has immunomodulatory effects (Petti, Bangrazi et al. 1998; Kaptchuk 2002). For example, T cells and activity of NK cells in cancer pa- tients treated with acupuncture have been shown to remain stable over the course of chemotherapy (Ye, Chen et al. 2002). In a group of relatively healthy young volunteers, acupuncture normalized leukocytes (Mori, Nishijo et al. 2002).

There are numerous modalities of healing that are theorized to involve the interaction of biomagnetic fields between two humans, one ªsendingº healing, the other ªreceivingº.

These include practices such as Reiki therapy, Johrei, Healing Touch, Therapeutic Touch, and laying on of hands in the context of prayer (Anderson 2001). Although practitioners from these various fields of practice may argue for marked differences in their intent and work, studies examining the biomagnetic fields emitted from the hands of healing prac- titioners across disciplines found similarity. Pulsing magnetic fields of extremely low fre- quency (ELF) emitted from the hands have been detected, the majority falling between 7±10 Hz with a range of 0.03 to 30 Hz (Zimmerman 1990; Seto, Kusaka et al. 1992). Sim- ilarly, healing practitioners using a variety of modalities also demonstrate similar EEG signatures while in the healing mode, altered state, or in prayerful focus (Beck 1986).

Although healing effects of emissions in these studies were not tested, the frequencies measured all fell into the same range as those electromagnetic device therapies shown to have specific healing outcomes (e.g., 7 Hz for bone growth, 15±20 Hz for capillary for- mation and fibroblast proliferation) (Sisken and Walker 1995).

Speculations about how healing interventions may work vary. One explanation is

that ªintentº may have an effect through the mind on the frequencies emitted and re-

ceived. Recent developments in the science of mind and experiments of consciousness are beginning to reveal effects for ªintentº on physical matter, such as re-configuration of water molecules (Tiller 1997). Another theory suggests that physical resonance de- velops via ªentrainmentº (an accepted principle in physics whereby pulsing of waves or rhythms produced by pendulums in close proximity will entrain to the point of res- onance) between the healer and target. Evidence of the potential for this explanation is provided in the work of Russek and Schwartz who show that even without intent for healing, two people sitting quietly with eyes closed in the same room will tend to couple both cardiac and brain wave rhythms (Russek and Schwartz 1994; Russek and Schwartz 1996).

The nature of human biofield-based energy healing has not been fully explained, but the effects have been well documented in randomized, controlled clinical trials on healing interventions such as Healing Touch, Therapeutic Touch and similar modali- ties. Despite continuing questions about exact modes of action, energy healing has been shown to significantly increase secretory immunoglobulin A (Wardell and En- gebretson 2001; Wilkinson, Knox et al. 2002), enhance immune system response (Quinn and Strelkauskas 1993; Ryu, Jun et al. 1995; Kataoka, Sugiyama et al. 1997) and produce relaxation or stress-reduction effects in general (Wirth, Cram et al.

1997). Other research has shown consistent results for improving quality of life and reducing stress-related symptoms in cancer patients undergoing treatment (Post- White, Kinney et al. 2003; Cook, Guerrerio et al. 2004). Although the application of the findings from these studies and the potential for cancer prevention has not yet been investigated, the results of these studies should attract enough attention to begin investigations of effects on biomarkers related to cancer risk or protection.

Large, randomized clinical trials that also allow for individualized treatment and practice plans, as is common in many forms of complementary and alternative medi- cine, do not currently fit research design standards in the U.S. Until research is able to be designed to encompass such studies, only small parts of this puzzle may be ex- amined to assess potential. One such puzzle piece may be the research that is begin- ning to emerge in the field of energy medicine through instruments designed to assess meridian flow.

Although the use of diagnostic methods such as ªseeingº imbalances in the human energy field (the mark of a Qigong master being the ability to see or detect Qi imbal- ances without the need of questioning, blood tests, or even hands-on pulse readings) may seem foreign to the western medical mind, there are recent developments in mea- surement of biofield emissions that correlate with and validate these fields. For exam- ple, acupuncture meridians and stimulation/collection points are detectable via instru- ments such as the MSA-21 that assesses electrical impedance along the meridians (Ro- berts 2002).

Instruments are available to assess flow of electrical potential across entire meri-

dians, such as the Gas Discharge Visualization device (GDV). The GDV captures the

biofield emissions surrounding each of the 10 fingers resulting in the measurement of

biophotonic discharge that is in direct proportion to the amount of energy flowing

through the 14 main meridians. The coronal discharges measured by the GDV are de-

tected as a result of the human bio-energy field interacting with the electrical field of

the device. At the time of measurement, the emitted light from the interaction is cap-

tured by a video camera, and then the images are analyzed with sophisticated software

using a mathematical tool known as fractal dimensionality. The data can be integrated over the whole body resulting in a quantifiable analysis of the energy flow and bal- ance throughout the meridian system (Korotkov 2002).

Experiments with the GDV in Russia have suggested potential for the detection of breast cancer. A study of 194 women, 140 with breast cancer, was conducted to assess the diagnostic potential of the GDV to see how it may be used to reflect the patient's ªenergy stateº in the process of chemotherapy, radiation therapy, and surgery. Statisti- cally significant differences were found between the GDV parameters of the cancer pa- tients when compared with a healthy control group. The patients with cancer had a wide range of stages and diagnoses (Korotkov 2002).

Despite growing evidence that biofields may be related to biological functions and may possibly precede material changes (Tiller, Dibble et al. 2001), it will take more rigorous research to define ways that protecting from assaults or correcting imbal- ances in those fields may affect health. There are experiments going on everyday through exposures and behaviors that we cannot fully understand the role of biofields in health until they are evaluated in randomized controlled trials.

Nevertheless, energy medicine practices are common throughout the world. In Chi- na, the largest population on earth practices Tai Chi daily to balance energy fields.

Although no correlation has yet been established, cancer rates in China are generally low (except for cancers directly attributable to tobacco) (Yuan, Ross et al. 1996). In fact, reviewing cancer rates worldwide, one might want to consider moving to Qidong, China as a ªbest practice for preventing cancerº! Very controversial evidence con- tinues to be wrestled with regarding exposure to electrical fields from power lines and cancer risk (Moulder and Foster 1995; Moulder and Foster 1999). The role of culture, health practices and spirituality, and many more suspects in the theatre of life expo- sures, need refined exploration. But until our understanding of mechanisms of ener- getic influences on the body and the biofield is understood in terms of the dominant microbiological paradigm, the research will neither be noticed nor applied to cancer prevention.

Conclusions

CAM is a continuously developing field, challenging researchers to find new epis- temologies to match complex systems and competing evidence. For example despite a long history of holding certain hormones responsible for hormone-related cancers, new evidence is accumulating on the potential of endogenous and/or bioidentical sup- plemental progesterone to have protective effects against several cancers (Cowan, Gor- dis et al. 1981; Formby and Wiley 1998; Malet, Spritzer et al. 2000; Horita, Inase et al.

2001; Dai, Wolf et al. 2002). As findings emerge from the cancer treatment realm, its

potential application to cancer prevention may be better understood. However, given

the many systems approaches to healing that may never be fully defined or researched

as a package, it may be important to find ways to investigate on a large scale what

cultural lifestyles and accompanying methods of healing used in those cultures, may

be associated with lower rates of cancer. It will be important to solve the problems of

separating out cultural and genetic influences on racioethnic populations and ruling

out spurious correlations from true effects and mediating factors in such observa-

tional studies. It may be necessary to develop an appropriate research paradigm to ap-

ply to trials on lifestyles that cannot be recreated or inhibited in real-life conditions, as is required in randomized controlled trials, before the potential for such systems is fully known.

In the meantime, smaller scale studies may begin to uncover select mechanisms of action of the elements of CAM. One of the primary funding agencies for examining alternative approaches to cancer treatment, control, and prevention of recurrence, the NCI's Office of Cancer Complementary and Alternative Medicine (NCCAM), has shifted many modalities previously considered CAM to conventional status. In partic- ular, the NCCAM now suggests that many of the mind-body approaches for reducing stress and improving quality of life among patients with cancer or cancer survivors has become mainstream due to well documented theoretical foundation and scientific evidence (e.g., patient education, biofeedback, and cognitive-behavioral approaches).

These mind-body approaches are now assigned to funding within the main body of NCI divisions unless the focus of research is more clearly placed on novel mechanisms of action for cancer that have yet to be investigated. Currently, both in the current re- search projects (NCI) and in the statements of the modalities suggested for investiga- tion (e.g., phase I/II trials of CAM mechanisms of action), it is evident that in the fu- ture, CAM approaches will be sorted out into those that can be scientifically validated and those that have less support. This is good news; as the consumer continues to ad- just lifestyle, seek wellness and attempt to prevent disease through conventional as well as alternative systems, knowledge that comes from well-designed research may guide this search toward more effective prevention strategies.

The creative search for alternative modes of treatment and supportive care for can- cer patients may serve as a useful starting point to identify potential candidate agents and practices for research in prevention. In this light, some of the therapies gaining popularity for supportive care may gain attention in the future as more than simply positive experiences. For example, music, art therapy, and guided imagery all have a long tradition of use with cancer patients, and many oncologists encourage their pa- tients to integrate such extra-medical practices into their treatment program. Often these are not seen as modalities that could affect the course of cancer, only to help the patients cope psychologically with their disease. However, as more evidence accu- mulates that such activities, even for healthy patients, might affect overall health and immunity, potentially even at the cellular level (Chopra 2000), these may also be ex- plored as ways to improve one's chances of avoiding cancer. Until that day, one should consider adding flaxseed and curcumin to a diet rich in fruits and vegetables, engage in some form of daily meditation, practice yoga, tai chi or qigong to the point of ob- taining a balanced GDV reading, and watch the research unfold over the next decade.

References

The Wellness Community (2004). Mission Statement.

Achterberg, J. and G. F. Lawlis (1984). Imagery and Disease: Diagnostic Tools? Champaign, Illi- nois, Institute for Personality and Ability Testing.

Achterberg, J., S. Mathews-Simonton, et al. (1977). ªPsychology of the exceptional cancer patient: a description of patients who outlive predicted life expectancies.º Psychother- apy: Theory, Research, Practice, Training 14: 416±422.

Ader, R., D.L. Felten, et al., Eds. (1991). Psychoneuroimmunology. San Diego, Academic Press.

Adlercreutz, H., T. Fotsis, et al. (1994). ªDetermination of lignans and isoflavonoids in plasma by isotope dilution gas chromatography-mass spectrometry.º Cancer Detect Prev 18(4):

259±271.

Adlercreutz, H., Y. Mousavi, et al. (1992). ªDietary phytoestrogens and cancer: in vitro and in vivo studies.º J Steroid Biochem Mol Biol 41(3±8): 331±337.

Agarwal, B., P. Swaroop, et al. (2003). ªCox-2 is needed but not sufficient for apoptosis in- duced by Cox-2 selective inhibitors in colon cancer cells.º Apoptosis 8(6): 649±654.

Anderson, E.Z. (2001). ªEnergy therapies for physical and occupational therapists working with older adults.º Physical and Occupational Therapies in Geriatrics 18(4): 38±49.

Astin, J.A., S.L. Shapiro, et al. (2003). ªMind-body medicine: state of the science, implica- tions for practice.º J Am Board Fam Pract 16(2): 131±147.

Bachelor, M.A. and G.T. Bowden (2004). ªUVA-mediated activation of signaling pathways in- volved in skin tumor promotion and progression.º Semin Cancer Biol 14(2): 131±138.

Beck, R. (1986). ªMood modification with ELF magnetic fields: a preliminary exploration.º Ar- chaeus 4: 48.

Becker, R.O. (1990). ªA technique for producing regenerative healing in humans.º Frontier Perspectives 1(2): 1±2.

Beebe-Dimmer, J.L., J. Wood, P. David et al. (2004). ªUse of complementary and alternative medicine in men with family history of prostate cancer: a pilot study.º Urology 63(2):

282±287.

Benjamin, H.H. (1995). The Wellness Community Guide to Fighting Recovery from Cancer.

New York, Putnam.

Benor, D. (1993). Healing research: Holistic Energy Medicine and Spiritual Healing. Munich, He- Benson, H. and E. M. Stuart (1993). The Wellness Book: the Comprehensive Guide to Maintain- lix.

ing Health and Treating Stress-related Illness. Secaucus, NJ, Carol Publishing Group.

Berland, W. (1995). Unexpected cancer recovery: Why patients believe they survive. Ad- vances: The Journal of Mind ± Body Health, Fetzer Institute. 11: 5.

Bernstein, B.J. and T. Grasso (1983). ªPrevalence of complementary and alternative medicine use in cancer patients.º Oncology (Huntington) 15(10): 1267±1272; discussion 1272±1278.

Boik, J. (2001). Natural Compounds in Cancer Therapy. Princeton, Minn., USA, Oregon Medi- cal Press.

Cadossi, R., G. Emilia, et al. (1988). Lymphocytes and pulsing magnetic fields. In: Modern Bioelectricity. A.A. Marino. New York, Dekker: xviii, 1050.

Cadossi, R., R. Iverson, et al. (1988). ªEffect of low-frequency low energy pulsing electro- magnetic fields on mice undergoing bone marrow transplantation.º International Journal of Immunopathology and Pharmacology 1: 57±62.

Cassileth, B.R. and G. Deng (2004). ªComplementary and Alternative Therapies for Cancer.º Oncologist 9(1): 80±89.

Chang, Y.S., E.K. Seo, et al. (2003). ªPanax ginseng: a role in cancer therapy?º Integr Cancer Ther 2(1): 13±33.

Chen, H.W., S.L. Yu, et al. (2004). ªAnti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis.º Mol Pharmacol 65(1):

99±110.

Chen, K. and R. Yeung (2002). ªA review of qigong therapy for cancer treatment.º Journal of International Society of Life Information Science 20(2): 532±542.

Chen, K.W., S.C. Shiflett, et al. (2002). ªA preliminary study of the effect of external qigong on lymphoma growth in mice.º J Altern Complement Med 8(5): 615±621.

Cherkin, D.C., R.A. Deyo, et al. (2002). ªCharacteristics of licensed acupuncturists, chiroprac- tors, massage therapists, and naturopathic physicians.º J Am Board Fam Pract 15(5):

378±390.

Chopra, D. (1989). Quantum Healing: Exploring the Frontiers of Mind/Body Medicine. New York, Bantam Books.

Chopra, D. (2000). Perfect Health: The Complete Mind-Body Guide. New York Three Rivers

Press.

Chu, K.K., S.S. Ho, et al. (2002). ªCoriolus versicolor: a medicinal mushroom with promising immunotherapeutic values.º J Clin Pharmacol 42(9): 976±984.

Cohen, K. (1997). The Way of Qigong=[Ch'i kung chi tao]: The Art and Science of Chinese En- ergy Healing. New York, Ballantine Books.

Conti, A. (2000). ªOncology in neuroimmunomodulation. What progress has been made?º Ann NY Acad Sci 917: 68±83.

Cook, C.A., J.F. Guerrerio, et al. (2004). ªHealing touch and quality of life in women receiv- ing radiation treatment for cancer: a randomized controlled trial.º Altern Ther Health Med 10(3): 34±41.

Cossarizza, A., D. Monti, et al. (1989). ªExtremely low frequency pulsed electromagnetic fields increase interleukin-2 (IL-2) utilization and IL-2 receptor expression in mitogen- stimulated human lymphocytes from old subjects.º FEBS Lett 248(1±2): 141±144.

Cowan, L.D., L. Gordis, et al. (1981). ªBreast cancer incidence in women with a history of progesterone deficiency.º Am J Epidemiol 114(2): 209±217.

Cunningham, A.J., C. Phillips, et al. (2000). ªAssociation of involvement in psychological self-regulation with longer survival in patients with metastatic cancer: an exploratory study.º Adv Mind Body Med 16(4): 276±287.

Cunningham, A.J., C. Phillips, et al. (2002). ªFighting for life: a qualitative analysis of the process of psychotherapy-assisted self-help in patients with metastatic cancer.º Integr Cancer Ther 1(2): 146±161.

Daaleman, T.P., S. Perera, et al. (2004). ªReligion, spirituality, and health status in geriatric outpatients.º Ann Fam Med 2(1): 49±53.

Dai, D., D.M. Wolf, et al. (2002). ªProgesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through pro- gesterone B receptors.º Cancer Res 62(3): 881±886.

Daniels, M., R.M. Merrill, et al. (2004). ªAssociations between breast cancer risk factors and religious practices in Utah.º Prev Med 38(1): 28±38.

Dattore, P.J., F.C. Shontz, et al. (1980). ªPremorbid personality differentiation of cancer and noncancer groups: a test of the hypothesis of cancer proneness.º J Consult Clin Psychol 48(3): 388±394.

Davidson, R.J., J. Kabat-Zinn, et al. (2003). ªAlterations in brain and immune function pro- duced by mindfulness meditation.º Psychosom Med 65(4): 564±570.

Demark-Wahnefried, W., D.T. Price, et al. (2001). ªPilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the ef- fects on hormonal levels, prostate-specific antigen, and histopathologic features.º Urol- ogy 58(1): 47±52.

Dibble, S.L., J. Chapman, et al. (2000). ªAcupressure for nausea: results of a pilot study.º On- col Nurs Forum 27(1): 41±47.

Eisenberg, D.M., M.H. Cohen, et al. (2002). ªCredentialing complementary and alternative medical providers.º Ann Intern Med 137(12): 965±973.

Eisenberg, D.M., R.C. Kessler, et al. (1993). ªUnconventional medicine in the United States.

Prevalence, costs, and patterns of use.º N Engl J Med 328(4): 246±252.

Elenkov, I.J. and G.P. Chrousos (2002). ªStress hormones, proinflammatory and antiinflam- matory cytokines, and autoimmunity.º Ann NY Acad Sci 966: 290±303.

Ell, K., R. Nishimoto, et al. (1989). ªA longitudinal analysis of psychological adaptation among survivors of cancer.º Cancer 63(2): 406±413.

Engelking, C. (1994). ªNew approaches: innovations in cancer prevention, diagnosis, treat- ment, and support.º Oncol Nurs Forum 21(1): 62±71.

Fields, J.Z., Rawal, P.A., Hagen, J.F., Ing, T., Wallace, R.K., Tomlinson, P.F., Schneider, R.H.

(1990). ªOxygen free radical (OFR) scavenging effects of an anti-carcinogenic natural product, Maharishi Amrit Kalash.º The Pharmacologist 32(3): 155.

Fisher, B., J.P. Costantino, et al. (1998). ªTamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.º J Natl Cancer Inst 90(18): 1371±1388.

Fisher, M. and L.X. Yang (2002). ªAnticancer effects and mechanisms of polysaccharide-K

(PSK): implications of cancer immunotherapy.º Anticancer Res 22(3): 1737±1754.

Formby, B. and T.S. Wiley (1998). ªProgesterone inhibits growth and induces apoptosis in breast cancer cells: inverse effects on Bcl-2 and p53.º Ann Clin Lab Sci 28(6): 360±369.

Friedman, M. and R.H. Rosenman (1974). Type ABehavior and Your Heart. New York, Knopf.

Fullerton, S.A., A.A. Samadi, et al. (2000). ªInduction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).º Mol Urol 4(1): 7±13.

Funch, D.P. and J. Marshall (1983). ªThe role of stress, social support and age in survival from breast cancer.º J Psychosom Res 27(1): 77±83.

Gaab, J., N. Blattler, et al. (2003). ªRandomized controlled evaluation of the effects of cogni- tive-behavioral stress management on cortisol responses to acute stress in healthy sub- jects.º Psychoneuroendocrinology 28(6): 767±779.

Garssen, B. and K. Goodkin (1999). ªOn the role of immunological factors as mediators be- tween psychosocial factors and cancer progression.º Psychiatry Res 85(1): 51±61.

Goodwin, P.J., M. Leszcz, et al. (2001). ªThe effect of group psychosocial support on survival in metastatic breast cancer.º N Engl J Med 345(24): 1719±1726.

Gordon, J.S. and S.R. Curtin (2000). Comprehensive Cancer Care: Integrating Alternative, Com- plementary, and Conventional Therapies. Cambridge, Mass., Perseus.

Grossman, H.B. (2003). ªSelective COX-2 inhibitors as chemopreventive and therapeutic agents.º Drugs Today (Barc) 39(3): 203±212.

Gruber, B.L., N.R. Hall, et al. (1988). ªImmune system and psychological changes in meta- static cancer patients using relaxation and guided imagery: a pilot study.º Scandinavian Journal of Behavior Therapy 17: 25±46.

Haggans, C.J., A.M. Hutchins, et al. (1999). ªEffect of flaxseed consumption on urinary estro- gen metabolites in postmenopausal women.º Nutrition & Cancer 33(2): 188±195.

Haggans, C.J., E.J. Travelli, et al. (2000). ªThe effect of flaxseed and wheat bran consump- tion on urinary estrogen metabolites in premenopausal women.º Cancer Epidemiol, Bio- markers Prev 9(7): 719±725.

Hahn, R.C. and D.B. Petitti (1988). ªMinnesota Multiphasic Personality Inventory-rated de- pression and the incidence of breast cancer.º Cancer 61(4): 845±848.

Hammerschlag, C. and H. Silverman (1997). Healing Ceremonies: Creating Personal Rituals for Spiritual, Emotion, Physical and Mental Health. New York, Perigee.

Hammerschlag, C.A. (1988). The Dancing Healers: ADoctor's Journey of Healing with Native Americans. San Francisco, Harper & Row.

Herron, R.E. and J.B. Fagan (2002). ªLipophil-mediated reduction of toxicants in humans: an evaluation of an ayurvedic detoxification procedure.º Altern Ther Health Med 8(5): 40±51.

Hirano, T., K. Fukuoka, et al. (1990). ªAntiproliferative activity of mammalian lignan derivatives against the human breast carcinoma cell line, ZR-75-1.º Cancer Invest 8(6): 595±602.

Hislop, T.G., N.E. Waxler, et al. (1987). ªThe prognostic significance of psychosocial factors in women with breast cancer.º J Chronic Dis 40(7): 729±735.

Holland, J.C. (1989). Behavioral and psychological risk factors in cancer: human studies. In:

Handbook of Psychooncology: Psychological Care of the Patient with Cancer. J.C. Holland and J. H. Rowland. New York, Oxford University Press. xiv, 785.

Horita, K., N. Inase, et al. (2001). ªProgesterone induces apoptosis in malignant mesothelio- ma cells.º Anticancer Res 21(6A): 3871±3874.

Hutchins, A.M., M.C. Martini, et al. (2001). ªFlaxseed consumption influences endogenous hormone concentrations in postmenopausal women.º Nutrition & Cancer 39(1): 58±65.

Ikemi, Y., S. Nakagawa, et al. (1975). ªPsychosomatic consideration of cancer patients who have made a narrow escape from death.º Dynamic Psychiatry 8: 77±91.

Johnson, J.A. (2000). Chinese Medical Qigong Therapy: AComprehensive Clinical Text. Pacific Grove, CA, The International Institute of Medical Qigong.

Jones, B.M. (2001). ªChanges in cytokine production in healthy subjects practicing Guolin Qigong: a pilot study.º BMC Complement Altern Med 1(1): 8.

Kaasa, S., A. Mastekaasa, et al. (1989). ªPrognostic factors for patients with inoperable non- small cell lung cancer, limited disease. The importance of patients' subjective experience of disease and psychosocial well-being.º Radiother Oncol 15(3): 235±242.

Kabat-Zinn, J. (1994). Wherever You Go, There You Are: Mindfulness Meditation in Everyday

Life. New York, Hyperion.