Traditional Chinese Medicine in the Treatment of Breast Cancer Isaac Cohen, LAc, OMD, Mary Tagliaferri, MD, LAc & Debu Tripathy, MD This is part one of a series of five articles designed to explore the integration of traditional Chinese medicine (TCM) in the treatment of breast cancer. Part one will detail the results of clinical trials from China. Part two will detail specific TCM and western medicine (WM) treatments for early stage breast cancer. Part three will discuss secondary prevention of breast cancer and part four will outline TCM pattern differentiation for breast cancer pathogenesis. The series will relate what is known scientifically as well as the authors clinical experience and current understanding of the disease. It will start with dry facts and culminate with the experiential and speculative. Abstract Back to the Table of Contents The treatment of breast cancer involves multiple disciplines, and current recommendations are based on modern tenets of biology and pharmacology along with a growing body of evidence based literature. Despite advances in screening, surgery, adjuvant radiation and systemic therapy and novel biologically targeted therapies, there are limitations to their benefits, especially in advanced disease. Complementary therapies including Oriental medicine have enjoyed a growing popularity as a less intensive and more natural approach to achieving health or improving quality of life. However, definitive literature in this area is scant and therefore has not been integrated into the mainstream medical community. Traditional Chinese medicine (TCM) may serve as a useful model for scientific inquiry since there is a standardised system of diagnostics and therapies, and this discipline is practised worldwide. Still, the holistic and individualised nature of TCM presents challenges to rigorous clinical testing, and as a result, most published work in this field is in the form of anecdotal reports or uncontrolled series. Among the components of TCM, herbal or botanical agents possess complex biological activities that could affect many aspects of carcinogenesis such as cell growth and proliferation, host-tumour interactions, immune function and differentiation. Despite a fairly extensive series of laboratory studies detailing many biological effects of botanical agents, few clinical trials have been completed to test specific hypotheses regarding the mode of action of TCM. Most TCM therapies have been empirically applied in a series of patients with descriptive results provided. The summaries of a few studies highlighted in this review can provide some evidence of safety but generally do not possess the design and results to verify clinical effectiveness. Nevertheless, the theory of TCM coupled with laboratory studies and safety information can serve as the basis for the design of more definitive trials of TCM for specific indications in breast cancer. There is increasing interest and growing opportunities for investigative approaches that could ultimately verify or reject TCM and specific botanical agents. Some of these initiatives in the area of breast cancer prevention and treatment are outlined. Introduction Back to the Table of Contents Many individuals with breast cancer seek alternative approaches to prevent recurrence and for the treatment of metastatic disease. Alternative approaches to medicine are widely used in the United States and throughout the world to treat a broad spectrum of conditions as well as to maintain wellness. It is estimated that one in two (46.3%) Americans currently use alternative therapies and make 629 million visits to alternative medicine practitioners each year. 1,2 Despite widespread use, complementary and alternative medical approaches have not undergone rigorous clinical testing to measure outcomes. Consequently, while more patients are seeking alternative medicine, there is little in the medical literature to determine if these therapies can be used safely, improve quality of life or provide a therapeutic benefit. Botanical agents were once the most significant medicinal substances employed by physicians. According to a WHO survey, 80% of the world population still rely on herbal medicine as their primary source for therapy.3 In the Western world, approximately 25% of currently prescribed drugs were first identified in higher plants4 and over half of the 50 most popular drugs today are derived from plant material.5 Over 60% of chemotherapeutic agents used in the treatment of cancer today are derived from natural substances6 and some of the most popular drugs are still fractionated from plant material.7 Chinese medicine employed treatments for cancer for over two millennia. The book The Rites of the Zhou Dynasty (1100- 400 BCE) refers to physicians specialising in the treatment of swellings and ulcerations or necrosis and ulcerations. These terms are still utilised in the modern practice of traditional Chinese medicine to denote the study and treatment of tumours that are both benign and malignant.8 Early Chinese medical texts described different types of breast tumours and discussed their clinical appearance, physiological origin and severity.8-11 Over 100 names were recorded for tumours in early medical literature. Most of these terms represent conditions that would be regarded as early cancerous conditions in the Western medical literature. The most frequently cited term for breast cancer was breast rock12. In the Yellow Emperors Classic of Internal Medicine (written circa 250 BCE), the first clinical picture of breast cancer was described. The prognosis was estimated to be approximately ten years after diagnosis and the process of progression, metastasis and death was detailed. 9 There are hundreds of anecdotal case reports of breast cancer cures using traditional Chinese medicine (TCM) as a sole therapy.13-15 Chinese medicine is useful in all stages of the disease to augment the benefits of conventional treatments, to prevent recurrence and metastasis in early stages of breast cancer, and to promote health, improve quality of life and prolong life in advanced stages.16-29 Method Back to the Table of Contents A wide literature search was conducted through the National Medical Libarary, the library of Shanghai University of Traditional Chinese Medicine and the library of Beijing Medical University. Key words used in the search were: breast cancer, TCM, acupuncture and herbal medicine. The search was conducted for all citations in these categories from 1984-2000. Most citations were either personal experiences and case reports of individual physicians, or of laboratory experiments using herbal medicine. For this review we accepted only controlled clinical trials or case controlled studies. Original sources were obtained mostly in the Chinese language by our collaborator Li Ping Ping M.D., Director of TCM Research Center at the Beijing Medical University, Cancer Research Institute, Beijing, P.R.C. and were translated by Shelley Oachs, M.Sc., L.Ac., a professional medical translator and licensed acupuncturist in San Francisco, California. Most of the studies reported in this review lack the accepted rigor required by Western medical journals yet the results are compelling and deserve further attention. Prevention: the treatment of breast cysts Back to the Table of Contents Although the number of cases of breast cancer has increased dramatically over the last decade in China30 the risk of being diagnosed with breast cancer or dying from breast cancer is still five times higher in Western countries than in China.31,32 Some of the differences are attributed to difference in body mass, age of onset of menstruation, length of menses and nutritional factors such as soy and green tea consumption.33 There are many case reports from China detailing effective treatments of breast disorders using herbal medicine and acupuncture. Some of these disorders are considered to increase the risk of breast cancer incidence. In the Western world 7% of women develop palpable breast cysts.34 Studies that included only or mainly women with palpable breast cysts have shown that those women are at an increased risk of developing breast cancer.35-38 The risk was age dependent but was independent of the type of cyst found.39 Dixon et al. showed that the overall standardised incidence rate of breast cancer in patients with palpable cysts was 2.81 (95%) when compared to the risk in the overall population. For women under 45 years old, the risk for developing breast cancer was the greatest at 5.94 (2.97- 10.63), with significant trend for decrease in relative incidence rate with age. The standardised risk was highest in the first year after aspiration of the cyst, 7.02 (3.73-12.00) but was still raised after five years, 2.68 (1.84- 3.76). Though there is no study that correlates the reduction or disappearance of palpable breast cyst with the reduction of breast cancer risk, one can speculate such a correlation. Five studies including 757 women (participation in the studies was as follows: n=389, 90, 50, 128, 100) aged 13-55 with a history of chronic fibrocystic breast disorder (FBD) and discrete palpable lump treated with Chinese herbal medicine that were discovered in our literature search are hereby summarised. FBD was defined by the presence of pain, cysts and distinct lumps, and patients enrolled in the studies were treated for one to six months. The average total effective rate, defined as complete resolution of lumps, pain and cystic changes for at least three months following herbal treatment, was 68.4% (518 women). When the 159 women who had partial effect defined by marked improvement of greater than 50% were included, the total effective rate of the herbal treatment was 89.4% (677 women). The herbal formulas used in the trials varied (see Table 2) and their therapeutic classification was defined according to TCM tenets.40 In a sixth trial, 120 women with discrete benign breast lumps were treated with traditional Chinese herbs. Radiological assessment (X-rays, ultrasound, thermography) were used for evaluation and diagnosis. Various herbal formulas (see Table 3) were administered according to differentiation of symptoms and signs based on the diagnostic principles of TCM. The age range was 20-62 years, with an average age of.41 Seven women were reported to be unmarried and 113 were married (denoting seven women were not sexually active). The patients were only permitted to take herbs that were prescribed in the clinical trial. In order to standardise the dose, the herbs were encapsulated and administered to the study subjects. A total of 46/120 (38.3%) women had complete resolution of the lumps for at least 3 months; 56/ 120 (46.6%) had greater than 50% reduction of the lumps, 12/120 (10%) had less than 50% reduction and 6 (5%) had no improvement. One treatment course comprised three months of herbal therapy. Complete resolution of symptoms after one course of treatment (three months) was experienced by 36/120 (30%) women and 10/120 (8.7%) had a complete resolution after 6 months. No adverse side effects were experienced by the participants.41 Results from a clinical trial of 96 women with breast lumps showed acupuncture and herbal medicine were effective in resolving the breast lumps and pain associated with fibrocystic syndrome.42 The participants were prescribed a single herbal formula (Modified Er Xian Tang, below) and they received acupuncture treatments at various locations on the Stomach and Liver channels, and the Governing and Conception vessels. Of the 96 women, 58 (60.4%) had complete resolution of the lumps after three months follow-up, and 17 (17.7%) were markedly improved. The total effective rate of the trial was 78.1%. The selection of the acupuncture points was based on combining points traditionally used for breast disorders and points that have shown to regulate specific reproductive hormone levels. The authors noted that the serum hormone analysis before and after the trial showed a regulation of the hypothalamus-pituitaryovarian axis. There was a decrease in serum estradiol and an increase in serum progesterone and testosterone. The authors speculate, on the basis of animal and human experiments, that acupuncture regulates hormonal function via neurohormonal and nervous reflex effects. This theory implies that the insertion of needles at specific acupuncture points can result in a secretion of neuro-chemicals or synaptic stimulation that have a down stream effect on secretory glands and cellular hormone receptors. In many of the clinical trials, modulation of oestrogen, progesterone and FSH were detected after the stimulation of acupuncture points. Modified Er Xian Tang Xian Mao (Rhizoma Curculiginis Orchioidis) 10g, Yin Yang Huo (Herba Epimedii) 12g, Chai Hu (Radix Bupleuri) 12g, Dang Gui (Radix Angelicae Sinensis) 15g, Bai Shao (Radix Paeoniae Lactiflorae) 10g, Gou Qi Zi (Fructus Lycii Chinensis) 10g, Lu Jiao Jiao (Colla Cornu Cervi) 15g, Zhi Gan Cao (Radix Glycyrrhizae Praeparatae) 5g. One bag a day in water decoction. Thirty bags to one treatment course. Increased mammographic breast density is an important surrogate marker of increased breast cancer risk. Increased breast density is seen more in younger, premenopausal women and women who use HRT.43-46 Women who consume more soy products have lower overall mammographic breast density.47 Mandelson et al.48 report that after adjustment for age at index mammogram (the mammogram used for the study), menopausal status, use of HRT and body mass index (BMI) the odds ratio (OR) for interval cancer (getting cancer within five years of dense mammogram) among women with extremely dense breasts is 6.14 (95%) comared to women with extremely fatty breasts. When only retrospective review of index mammogram were considered, without adjusting to age, which is one of the most significant risk factors for breast cancer, the OR increased to 9.47 (95%). A study of 460 women with benign breast lumps and increased breast density treated with herbs reported a good effect on the resolution of lumps and reduction of density. The women in the trial ranged in age from 19-58, with an average age of 38.5; 79.6% were between the ages of 28-45 years and 20.4% were 46-58 years old. Among those enrolled in the study, 206 of the women suffered from bilateral breast lumps and increased density, 148 had the symptoms on the left only and 106 had symptoms on the right. All the patients were followed for six months after the end of the treatment. The patients were classified into three groups according to TCM pattern differentiation and were given a single herbal formula (Xiao He Ling Formula, below). Of the 460 women, 108 (23.5%) showed complete response. Complete response was defined as the complete disappearance of lumps and shadows with X-ray and infra-red ray assessments. A total of 222/460 (48.3%) women showed marked improvement (greater than 50% reduction) and 96/460 (20.9%) of women showed some improvement (defined greater than 50% reduction of density but less than 50% reduction of the mass).49 Xiao He Ling Formula Wu Gong (Scolopendra Subspinipes), Yan Hu Suo (Rhizoma Corydalis Yanhusuo), Chuan Sha Jia (Squama Manitis Pentadactylae), Quan Xie (Buthus Martensi), Yu Jin (Tuber Curcumae). Unfortunately none of the above data has been directly correlated to a reduction in the incidence of breast cancer. Patient follow-up was relatively short and no information about the incidence or risk of breast cancer was reported. The Treatment of Breast Cancer Back to the Table of Contents Breast cancer is currently treated with surgery, adjuvant and neo-adjuvant chemotherapy of short duration (3-6 months), local irradiation, biological agents and long-term hormonal therapy (up to 5 years). The effects of those treatments have been defined and characterised widely through large randomised controlled clinical trials in the past decades. The use of clinical trials methodology helped oncologists clarify the actuarial usefulness of the treatments employed and therefore strategise the treatment in accordance with both clinical and molecular findings. The use of adjuvant chemotherapy has shown a significant decrease in both the rate of recurrence and in mortality. In their meta-analysis of breast cancer adjuvant chemotherapy clinical trials, The Early Breast Cancer Trialists Collaborative Group reported that adjuvant chemotherapy produced significant proportional reductions in breast cancer recurrence for both women under the age of 50 (35% reduction) and for women 50-69 years of age (20% reduction). The recurrence reduction was chiefly observed in the first 5 years of follow-up. Mortality was significantly reduced for women under 50 (27% reduction ) and among women 50-69 years of age (11% reduction). The difference in survival grew throughout the first 10 years. For women under 50 years old with node-negative disease the 10 year absolute survival benefit was 7% (from 71%-78%) while for women with nodepositive disease the 10 year absolute survival benefit was 11% (from 42%-53%). For women 50-69 years of age with node negative disease the 10 year absolute survival benefit was only 2% (from 67%-69%) while for those women with nodepositive disease the 10 year absolute survival benefit was 3% (from 46%-49%)50. Since most women who are diagnosed with breast cancer are older than 50 years of age51 the mortality benefit is less statistically significant for the majority of women diagnosed with breast cancer. The current trend in China is to integrate, or combine, Western therapies with TCM in the treatment of breast cancer. There are no available statistics on the proportion of women using this approach. Our collaborators in China estimate that about 70%-80% of women diagnosed with breast cancer in the metropolitan areas, where Western medicine (WM) is favoured, are using the combined approach at some point during their treatment of breast cancer while a very small fraction of women use TCM as a sole therapy (private conversations with Dr. Li Ping Ping and Dr. Yu GQ, President emeritus of All China Society of Cancer Prevention and Treatment with Integrated TCM and WM). The treatments employed by the TCM physicians are aimed at controlling side effects and toxicities attributed to cancer therapies, improving quality of life, preventing recurrence and prolonging survival.52-54 Conclusion Back to the Table of Contents The results reported in this survey are very compelling. A direct effect of integrated WM and TCM on both recurrence- free survival and overall survival are noted. Though we tried to include only well documented studies, they all suffer from many major methodological and reporting flaws that leave many questions to a critical reader rather than clear answers. It has already been noted by several researchers that clinical reports from China tend to produce only positive results.67,68 Compared to trials published in England where 75% gave the test treatment superior results to control, the results in China were 99% superior to controls.67 The reports generally suffer from writers bias. Botanical/herbal medicine is one of the more popular complementary and alternative medical approaches used by cancer patients. Chinese herbal therapy is a treatment modality widely sought by breast cancer patients.69,70 Many women diagnosed with breast cancer use Chinese herbal therapy both as anti-cancer agents as well as to alleviate the side effects of chemotherapy and of the cancer itself. Traditional Chinese medicine (TCM) is also well suited to investigation using a Western clinical model because there is a high degree of conformity about both diagnoses and treatments among practitioners, extensive texts exist to facilitate research, and practitioners are licensed to dispense herbs in many US states. Therefore, it is essential that a scientifically sound methodology be developed to evaluate the specific benefits and risks associated with Chinese herbal therapy for breast cancer. For reasons of space,this series has been extended to five parts. Part three will discuss the use of Chinese medicine in the context of chemotherapy; part four will discuss secondary prevention of breast cancer, and part five will outline the TCM differentiation for breast cancer pathogenesis. (Part Two) Traditional Chinese Medicine in the Treatment of Breast Cancer Abstract Back to the Table of Contents Traditional Chinese medicine (TCM)is becoming increasingly popular in many medical contexts, particularly among patients with cancer. TCM encompasses a range of modalities including herbal medicine, acupuncture, medical qigong, dietary recommendations and meditation (daoyin ). In contrast to standard chemotherapeutic and hormonal regimens used for the adjuvant treatment of early stage breast cancer, very little data from controlled clinical trials has been generated using TCM modalities in relationship to the outcomes of recurrence or survival,or even overall quality of life and safety. As we previously reported 1 , the objectives of TCM modalities are manifold - the reduction of therapeutic toxicity, improvement in cancer-related symptoms, improvements in the immune system, and even a direct anti-cancer effect. The primary basis of TCM rests upon empirical evidence and case studies, as well as its theoretical principles.In some cases, laboratory or clinical data lend support to these modalities. Although TCM practices are based on ancient medical tenets founded on centuries of experience, and documented through oral and written texts, its direct relationship to breast cancer treatment in an integrative setting is very young. There is still a paucity of evidence in the clinical setting, which limits firm conclusions about the effectiveness or safety of most TCM approaches to breast cancer. This review will summarise the application of certain TCM modalities in the therapy of early stage breast cancer. Introduction Back to the Table of Contents Cancer affects one in three individuals in the Unites States and most patients seek initial evaluation and therapy in the modern conventional setting. Most oncologic therapies are based on evidence from randomised trials showing improvements in outcomes, particularly survival. However the use of TCM is becoming increasingly prevalent both where few conventional therapeutic or ameliorative options exist and also because standard oncologic therapies have side effects that can significantly affect patients' short and long term quality of life. A review of surveys of cancer patients from around the world showed the average prevalence of complementary and alternative medicine (CAM) use was 31%, with the most common types cited being dietary treatments, herbs, homoeopathy, hypnotherapy, imagery/visualisation, meditation, megavitamins, relaxation and spiritual healing 2 . In China many hospitals that have cancer wards offer TCM treatments alongside Western treatments, although there is no formal study addressing the use of TCM among cancer patients. Colleagues in China estimate that in rural areas almost all patients take herbal medicine when treated for cancer,while in urban areas that number is estimated to be 50%-60%, with increase of use in more advanced stages of the disease. A population-based study conducted in San Francisco, California showed that 72%of women with breast cancer used at least one form of complementary or alternative medicine,and one third used two forms 3 . The types of approaches used included dietary therapies (26.6%, including megavitamins), spiritual healing (23.7%), herbal remedies (12.9%),physical methods (14.2%),and psycho- logical methods (9.2%).4 The use of herbal medicine among women with ovarian cancer was 51% while only 12% of the women used trained herbalists for guidance. 5 Use of CAM was more common in younger women, more educated individuals, and among women with advanced stages of cancer; about half of the patients reported the usage of CAM modalities to their physicians. The complete abandonment of conventional therapy accompanying the use of alternative approaches is not very common despite the fact that conventional and alternative medicine in the Western world are almost never administered in a coordinated fashion. 6 Most formally trained medical oncologists tend to avoid making recommendations in the areas of alternative medicine and are generally reluctant to integrate their treatment plan with a discipline that is foreign to their training and not represented in the scientific literature. Yet at the same time, increasing awareness of CAM,coverage by the lay press and intense presence through electronic media, especially via the internet, has amplified cancer patients' interest in and pursuit of CAM. A recent analysis of over 1,000 CAM studies for breast cancer published in the mainstream biomedical literature however revealed few controlled,well designed studies with adequate endpoints. 7 Several TCM modalities have been highlighted for discussion of their potential study and applicability in the area of adjuvant therapy for early stage breast cancer. Of these, special emphasis is placed on herbal medicine and acupuncture given their prevalent use in China and by Western practitioners. Traditional Chinese Medicine Back to the Table of Contents Traditional Chinese Medicine (TCM) serves as a useful yet complicated model of CAM therapy in a variety of medical settings.TCM consists of herbal medicine that is usually administered as a combination or formula,as well as acupuncture. Therapy is typically individualised on the basis of a TCM diagnosis of imbalance of the body measured by various parameters including yin,yang,qi,blood and body fluids. TCM diagnoses generally do not follow standard Western pathophysiologic classifications of disease. The tradition of TCM has evolved and been passed down for centuries and several well recognised texts and training institutions exist; hence, there is a fair degree of standardisation of diagnostic and therapeutic practice. Furthermore, TCM practice is licensed and regulated in most US states. Given the widespread use of TCM on the West coast of the United States, our research program has focused on this modality for clinical investigation in several settings for breast cancer. Although a significant body of research has been conducted in China into the ability of TCM to treat cancer, many of the studies are of poor quality, lack proper control groups, fail to describe the specific methods of the study and omit information about the statistical significance of the results. An overview of both acupuncture and herbal medicine studies in specific cancer-related settings is presented here as it applies to the potential for the study of TCM in early stage breast cancer in conjunction with and following chemotherapy or radiation therapy. TCM intervention for surgery Back to the Table of Contents Surgery is by far the most effective treatment for early breast cancer and all women diagnosed with early breast cancer will undergo surgery as the main treatment for the disease. Currently women face several surgical options when encountering breast cancer diagnosis: lumpectomy with or without axillary lymph node excision (axillary clearance) or sentinel node excision,or modified radical mastectomy. Surprisingly there is no significant survival benefit to mastectomy over lumpectomy followed by locoregional radiotherapy. In recent years women who are diagnosed with large breast tumors, for whom lumpectomy is impractical for cosmetic reasons, have undergone neo-adjuvant chemotherapy, prior to surgery, in order to attempt to reduce the tumour size and conserve the breast. There is no significant difference in survival between women who undergo neo-adjuvant chemotherapy followed by surgery and women who undergo modified radical mastectomy 8-16 . From a TCM point of view surgery is considered as an externally inflicted wound that results in damage to the smooth flow of qi and blood, gives rise to qi deficiency and blood stasis and results in both accumulation of blood in the vessels and in inability of the Spleen qi to contain qi and blood. Anaesthesia disturbs the functions of the hun (ethereal soul) and po (corporeal soul) in commanding the distribution and correct response of qi and blood. While under normal circumstances the body would have reacted with pain and strong survival response elicited by a combination of voluntary and involuntary reactions, the artificial disturbance of anaesthesia on the the hun and po results in irregularity in the normal course of the flow of qi, resulting in shen disturbance, qi deficiency and blazing of yin fire. The resulting symptoms such as pain, bruising, immobility, nausea and vomiting are part of that syndrome. Although chemotherapy may induce nausea and vomiting as well, the type of symptoms and the duration of the symptoms encountered by women will be different. Post operatively the symptoms of nausea and vomiting tend to be shorter in duration: from a few hours to 3 days. The mechanisms of nausea and vomiting induction are not very clear. Many brain areas seem to be affected (area postrema, nucleus tractus solitarius and central pattern generator)and they are all mediated by abdominal vagal afferents. Pre-operative acupuncture Several issues can be addressed by TCM pre-and post- operatively.In preparation to surgery,acupuncture has been shown to reduce nausea and vomiting and pain. 17 Simple points like Hegu L.I.-4, Taichong LIV-3, Zusanli ST-36 and Neiguan P-6 have been used successfully for this purpose. Contraindicated herbs with anaesthesia Several anecdotal reports can be found in the literature of suspected negative interaction between anaesthesia control and herbs 18-19 and suggest that some caution should be practised.The following pharmacological categories are recommended to be used with caution: Anticoagulants Bai Zhu (Rhizoma Atractylodis Macrocephalae) Dan Shen (Radix Salviae Miltiorrhizae) Chuan Xiong (Radix Ligustici Wallichii) Antithrombics Dang Gui (Radix Angelicae Sinensis) Hong Hua (Flos Carthami Tinctorii) Jiang Huang (Rhizoma Curcumae) Yi Mu Cao (Herba Leonuri Heterophylli) CNS stimulating effect Jin Yin Hua (Flos Lonicerae Japonicae) Ma Huang (Herba Ephedrae) Ren Shen (Radix Ginseng) Coronary vasodilating and flow increasing Bai Guo Ye (Folium Ginkgo Bilobae) Bai Shao (Radix Paeoniae Lactiflorae) Bu Gu Zhi (Fructus Psoraleae Corylifoliae) Ji Xue Teng (Radix et Caulis Jixueteng) Hypertensives Sheng Jiang (Rhizoma Zingiberis Officinalis Recens) Chen Pi (Pericarpium Citri Reticulatae) Wu Yao (Radix Linderae Strychnifoliae) Platelet aggregation inhibitors Ge Gen (Radix Puerariae) Shan Zhu Yu (Fructus Corni Officinalis) Yan Hu Suo (Rhizoma Corydalis Yanhusuo) Yin Yang Huo (Herba Epimedii) Post-operative acupuncture Back to the Table of Contents Therapeutic and reconstructive surgeries bring on a variety of unwelcome conditions, including pain, anaesthesia-induced nausea,short-term diminished mobility, bruising and fatigue. TCM can be used to accelerate wound healing, increase peripheral blood circulation to aid the supply of nutrients and blood cells to the wounded area, aid nerve regeneration, reduce scarring, enhance the immune system and prevent lymphedema (swelling of the arm that can occur after the lymphatic vessels are severed by surgery). A preliminary study of post surgical nausea,vomiting and pain,conducted at Duke University 17 showed that acupuncture is slightly more effective than the most commonly used antiemetic, ondansetron (Zofran).40 women undergoing breast surgery (augmentation, reduction or mastectomy) requiring general anaesthesia were studied. The surgery lasted 2-4 hours. The results can be summarised as follows: Symptom Placebo Zofran Acupuncture Incidence of nausea at 2 hrs. post-op 69% 36% 23% Incidence of vomiting at 2 hrs. post-op 23% 7% 7% Incidence of nausea at 24 hrs. post- op 61% 57% 38% Incidence of vomiting at 24 hrs. post- op 46% 28% 23% Incidence of pain at 2 hrs. post-op 77% 64% 31% On the surface the results seem more than slightly better for the acupuncture treatment, but the number of women treated in this study was too small to derive a statistically significant conclusion. Other than postoperative nausea,vomiting and pain, acupuncture is very useful to relieve postoperative constipation. Points like Shangjuxu ST-37,Xiajuxu ST-39, Yanglingquan GB34,Zhigou SJ-6,Neiguan P-6,Tianshu ST-25, Qihai REN-6 and Qihaishu BL-24 seem to be very effective, especially when stimulated strongly. Acupuncture can be complemented with some herbs that stimulate bowel motility like Da Huang (Rhizoma Rhei)and Huang Lian (Rhizoma Coptidis).20-22 Gui Zhi Jia Shao Yao Tang (Cinnamon Twig Decoction plus Peony)may also be used. Post-operative herbal interventions to help wounds heal and stimulate platelet aggregation herbs such as Huang Qi (Radix Astragali) are used 23 , whilst herbs that inhibit granulation,such as Ba Ji Tian (Radix Morindae Officinalis)24 , should be avoided. The application of herbal medicine after surgery takes into consideration the post-surgical syndrome, as described above, as well as the disease itself and the opportunity to initiate prevention of recurrence. Strengthening qi and fluids,regulating blood and reducing heat and toxins are the therapeutic principles employed. Breast Cancer Post-Operative Formula Herb name Dose in grams Xia Ku Cao (Spica Prunellae Vulgaris) 15 Dang Gui (Radix Angelicae Sinensis) 10 Zhu Ling (Sclerotium Polypori Umbellati) 15 Shan Ci Gu (Bulbus Shancigu) 6 Jin Yin Hua (Flos Lonicerae Japonicae) 12 San Qi (Radix Pseudoginseng) 1.5 Huang Qi (Radix Astragali) 15 Tai Zi Shen (Radix Pseudostellariae Heterophyllae) 15 Gua Lou (Fructus Trichosanthis) 20 Fu Ling (Sclerotium Poriae Cocos) 15 Zi He Che (Placenta Hominis) 12 Bai Shao (Radix Paeoniae Lactiflorae) 10 Tian Men Dong (Tuber Asparagi Cochinchinensis) 15 Bai Hua She She Cao (Herba Oldenlandiae Diffusae) 15 Ren Shen (Radix Ginseng) 5 Zhi Mu (Radix Anemarrhenae Asphodeloidis) 12 TCM and radiation treatment Back to the Table of Contents Radiation is another prevention method for early breast cancer.The application of high energy beams through the breast tissue and local lymph nodes reduces the probability of local recurrence. 25-28 Radiation exerts its cell inhibitive effect through the creation of a high concentration of free radicals that create high local oxidative stress. The oxidative stress causes irreparable DNA damage and results in cell death. Since the cell death caused by radiation is not selective to cancer cells the whole radiated area is affected and the body responds to it with strong inflammatory reaction. The main side effects of radiation are fatigue accompanied by agitation and insomnia. TCM views radiation as an extreme external attack of heat and dryness which,as with sun exposure, damages the yin fluids and the Spleen qi, with local accumulation of heat, fire and toxins. Inhibition of the Spleen's ability to transform pure from impure and to propel the vapour from food results in a complex picture of heat-fire dryness above,stagnation of heat toxins locally and deficient damp-heat below. In order to increase the cell killing effect of radiation and control its local side effects,one needs to increase oxygenation to cells,and promote peripheral blood flow 29-34 . Herbs that are commonly used during radiation Anti-hypoxic effect (increase cell oxygenation): Dang Shen (Radix Codonopsis Pilosulae), Hong Hua (Flos Carthami Tinctorii), Bai He (Bulbus Lilii), Yin Yang Huo (Herba Epimedii). Microcirculation improving effect: Chuan Xiong (Radix Ligustici Wallichii), Dang Shen (Radix Codonopsis Pilosulae), Pu Huang (Pollen Typhae), Yi Mu Cao (Herba Leonuri Heterophylli). Antihistaminic effect (can reduce itching ,anti inflammatory effect can reduce swelling and redness in the breast and skin): Bai Zhi (Radix Angelicae),Qin Jiao (Radix Gentianae Macrophyllae), Jin Yin Hua (Flos Lonicerae Japonicae), Huang Qin (Radix Scutellariae Baicalensis). Radiation sensitizing effect: Ren Shen (Radix Ginseng), Ling Zhi (Ganoderma Lucidum), Gui Pi Tang (Restore the Spleen Decoction), Hong Hua (Flos Carthami Tinctorii). Two herbs [Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae)and Rou Gui (Cortex Cinnamomi assiae)]can inhibit radiation effect; when given to animals they increase their survival 32 Burns and skin protection To prevent radiation burns and rashes apply Aloe-Vera gel (fragrance-free,above 96%pure; fresh Aloe juice or leaf is superior) on the skin 2-3 times a day. If an itchy, red, rough sensation starts to develop apply Ching Wan Hung ointment, once or twice a day. Beware that it stains everything. For more severe burns apply the following formula externally: Da Huang (Rhizoma Rhei)30, Di Yu (Radix Sanguisorbae Officinalis)30, Hong Hua (Flos Carthami Tinctorii)20, Chuan Xiong (Radix Ligustici Wallichii)15, Long Kui (Herba Solani Nigri)20, Han Shui Shi (Calcitum) 12, Shi Gao (Gypsum)12. In cases of blistering and pus add Huang Bai (Cortex Phellodendri). Grind the above ingredients to very fine powder and mix with boiling water to make a light paste. Apply to burns with gauze, twice a day and leave on the skin for 30-60 minutes. Fatigue From the TCM perspective, radiation-induced fatigue is due to accumulation of heat toxin causing dryness and therefore disturbing the yin fluids. This in turn causes yin vacuity blazing fire. The symptoms are extreme fatigue accompanied by agitation and insomnia. This usually does not start until the third week into radiation therapy. Weekly acupuncture treatment relaxes this sort of agitation and comprehensive herbal therapy attempts to counter the damage to the fluids and the inflammation. Scarring Scarring from radiation is different from that of surgery. Since the radiation exposure covers a large area, the beams pass through and scatter to areas in the interior of the body, mainly the lungs and, if the cancer was in the left breast, to the heart. Though radiation technology has improved significantly in the last decade, preventing heart and lung fibrosis is important. Again the herbs we use are those that increase microcirculation, decrease collagen activity and promote the breakdown of scars, protecting the body from pulmonary fibrosis caused by radiation: Dan Shen (Radix Salviae Miltiorrhizae),Yu Jin (Tuber Curcumae) and Ji Xue Teng (Radix et Caulis Jixueteng). (Part Three) Traditional Chinese Medicine in the Treatment of Breast Cancer Abstract Back to the Table of Contents Traditional Chinese medicine (TCM) is becoming increasingly popular in many medical contexts, particularly among patients with cancer. TCM encompasses a range of modalities including herbal medicine, acupuncture, medical qigong, dietary recommendations and meditation (daoyin). In contrast to standard chemotherapeutic and hormonal regimens used for the adjuvant treatment of early stage breast cancer, very little data from controlled clinical trials has been generated using TCM modalities in relationship to the outcomes of recurrence or survival, or even overall quality of life and safety. As we previously reported1, the objectives of TCM modalities are manifold - the reduction of therapeutic toxicity, improvement in cancer-related symptoms, improvements in the immune system, and even a direct anti-cancer effect. The primary basis of TCM rests upon empirical evidence and case studies, as well as its theoretical principles. In some cases, laboratory or clinical data lend support to these modalities. Although TCM practices are based on ancient medical tenets founded on centuries of experience, and documented through oral and written texts, its direct relationship to breast cancer treatment in an integrative setting is very young. There is still a paucity of evidence in the clinical setting, which limits firm conclusions about the effectiveness or safety of most TCM approaches to breast cancer. This review will summarise the application of certain TCM modalities in the context of chemotherapy, enhancing immune function, and treating hematopoesis and peripheral neuropathy. TCM and chemotherapy Back to the Table of Contents We previously reported the clinical benefits of adjuvant chemotherapy in the treatment of early breast cancer.1-2 Although chemotherapy can be useful in the prevention of breast cancer recurrence and in reducing breast tumour size, its toxicity causes many adverse and unpleasant side effects which affect quality of life. The most common regimens that are in use in early breast cancer adjuvant chemotherapy are Doxorubicin (Adriamycin) with Cyclophosphomide (Cytoxan) [usually abbreviated to AC chemotherapy], Cytoxan, Methotraxate and 5- flourauracil (5-FU) [usually abbreviated to CMF] and Paclitaxel (Taxol) or Docetaxel (Taxotere). In recent years there has been a trend to integrate TCM treatment with standard western medicine in an attempt to further optimise the treatment outcomes, minimise the side effects of surgery, radiation and chemotherapy, increase immune function and improve survival. This form of treatment is known as Fu Zheng Therapy(FZ) or Support the Normal Qi FZ therapy is a comprehensive system of utilising traditional medical principles to affect the following goals: i. Tumour load reduction or antineoplastic effect. TCM treatment principles of antineoplastic action include: attacking, dissolving, moving, detoxifying, resolving pathogenic factors, warming, and cooling down the tumours. ii. Prevent the formation and development of cancer. TCM principles of treatment with anticarcinogenic and antimutagenic action include harmonising and strengthening nutritive and defensive qi and clearing pathogenic factors. iii. Modulate the immune system and prevent immune suppression by tonifying qi, blood, yin and yang, harmonising flow and distribution, and promoting production and metabolism of body fluids. iv. Enhance the regulating function of the endocrine system. Regulate the flow of qi, invigorate the flow of blood and tonify yang. v. Enhance and protect the structure and function of the organs. Tonify yin and yang of the viscera and bowels. vi. Strengthen the digestion and absorption of nutrients and improve metabolism. Invigorate, tonify and strengthen the Stomach and Spleen. vii. Protect bone marrow and haematopoietic function. Nourish and tonify essence. viii. Increase effectiveness of surgery, radiation, chemotherapy and hormonal therapy with herbs that lower drug resistance and increase peripheral blood flow. Harmonise the flow of qi, move and invigorate the flow of blood ix. Prevent, ameliorate and control adverse side effects (such as nausea and vomiting, fatigue, insomnia and pain) and diseases caused by cancer therapy (such as cardiac toxicity and hepatic toxicity). Protect the viscera, regulate qi, redirect the flow of qi and assist branch symptoms. 3-11 Many herbal decoctions have been designed to achieve the above-stated goals. The herbs are chosen according to both their traditional use and to some modern pharmacological and clinical research about them individually and in groupings. The therapeutic goal is to tailor the formula to the specific cancer, the chemotherapy agents and chemotherapy dose, whilst conforming with the individual's TCM diagnosis. As an example, during AC chemotherapy regimen, usually given in twenty-one day intervals for 4 cycles, the symptoms vary with individuals and with the progression of the therapy. Some women experience more symptoms at the initiation of the treatment while others more towards the end. Doses are monitored by weight, height and desired therapeutic purpose: i. From days 1-6 of chemotherapy, most of the AC agents are metabolised in the body and assume most of their cytotoxic activity. Erosion of epithelial mucous and serous membranes is the most noticeable effect, creating dry mouth, bleeding gums, ulceration and sores in the mouth, vomiting, nausea, loss of appetite, diarrhoea, constipation, abdominal pain and distention, cystitis, skin rashes and palpitations. More severe reactions are stomatitis, oesophagitis, pancreatitis, pericarditis, haemorrhagic cystitis and bleeding ulcers. The function of the herbal formula at this stage is to increase blood and lymphatic circulation to promote the distribution of the chemotherapy agents and to promote elimination of cell debris, nourish the yin to protect the mucous membranes, control nausea and vomiting, promote urination, direct the flow of qi downward, and promote appetite. ii. From days 7-12, most of AC's cytotoxic activity is accomplished, and the damage to the bone marrow and organs is at its peak. This stage is marked by fatigue, malaise, dizziness, insomnia, fever, arthralgia, cognitive vagueness (what women call chemo-head) poor circulation, alternating hot and cold sensations, unproductive cough, palpitations, tachycardia, bradycardia, anaemia, leukopenia and thrombocytopenia, and in rare severe incidents, cardiac toxicity, hepatic toxicity or renal toxicity. The role of the herbal formula in this stage is to tonify qi, blood, yin and yang, nourish essence, protect and restore the vital functions of the organs and the bone marrow, promote circulation, promote urination, enhance metabolism, harmonise defensive and nutritive energy in order to increase immunity, and prevent infections. iii. Days 12-21. At this stage the body is regenerating, eliminating and recovering its functions and structure. The symptoms and signs at this stage are improvement and recovery from all previous symptoms although fatigue, malaise, insomnia, joint pain, and cognitive vagueness may still occur. New symptoms may also appear, such as alopecia, hyper pigmentation of nail beds, and increased psychological and emotional reactions. The role of the herbal formula at this stage is to tonify qi, blood, yin and yang to promote the recovery and regeneration of the cells, bone marrow and organs, promote circulation and urination, and calm the spirit12 (see formulas). Modifications to all formulas 13-16 Back to the Table of Contents Constipation: Gua Lou (Fructus Trichosanthis), Da Huang (Rhizoma Rhei), Rou Cong Rong (Herba Cistanches). Diarrhoea: Huang Lian (Rhizoma Coptidis), Qin Pi (Cortex Fraxini), Hou Po (Cortex Magnoliae Officinalis). Insomnia: Suan Zao Ren (Semen Ziziphi Spinosae), Wu Wei Zi (Fructus Schisandrae Chinensis), Bai Zi Ren (Semen Biotae Orientalis), Mu Li (Concha Ostreae), Ye Jiao Teng (Caulis Polygoni Multiflori). Herbs to avoid in cases of insomnia: Ma Huang (Herba Ephedrae), Fu Zi (Radix Aconiti Carmichaeli Praeparatae), Ren Shen (Radix Ginseng) at night, Zhi Shi (Fructus Citri seu Ponciri Immaturus), Jin Yin Hua (Flos Lonicerae Japonicae). Mouth sores and loss of sense of taste (used as a mouth rinse): Hu Lu Ba (Semen Trigonellae Foeni-graeci), Wu Zhu Yu (Fructus Evodiae Rutaecarpae). Acupuncture for chemotherapy-induced nausea and vomiting Back to the Table of Contents There is a substantial amount of scientific literature that supports the efficacy of both acupressure and acupuncture to treat chemotherapy-induced nausea and vomiting. In 1997, the strength of the scientific evidence for this application led the 12-member US National Institutes of Health (NIH) consensus panel on acupuncture to conclude that needle acupuncture treatment is effective for postoperative and chemotherapy nausea and vomiting17. This led to a special request for applications (RFA) by the NIH for research projects in the area of acupuncture for indications including pain due to cancer and nausea associated with chemotherapy. Chemotherapy-induced nausea and vomiting continues to be one of the most frequent, severe and distressing side effects endured by cancer patients. In chemotherapy regimens used for early stage breast cancer, 30-40% of patients still experience nausea and vomiting within 1 week of chemotherapy administration, even with the use of newer seratonin receptor antagonists.18-19 In some cases, these side effects make a difference in the choices patients and physicians make and can also lead to early discontinuation or dose reductions of chemotherapy. Modalities such as relaxation, visualisation and acupuncture have historically been used as an adjunctive to nausea in many settings. Much of the scientific literature regarding acupuncture for nausea and vomiting, including the setting of chemotherapy administration, has been published by J.W. Dundee and his colleagues at the Queen's University of Belfast20-26. In his studies, Dundee evaluates the role of the most widely used acupuncture point for nausea and vomiting, Neiguan P-6. Dundee's initial comparative studies examined the antiemetic effect of Neiguan P-6 in 105 patients who had a history of nausea and vomiting in a previous round of chemotherapy. This study reported a 63% anti-emetic benefit from the acupuncture. Findings from a smaller, single blind, crossover study provide evidence that the beneficial effects were limited to the specific acupuncture point Neiguan P-6 when compared to a dummy or sham acupuncture point25. Subsequent wellcontrolled studies have similarly shown that acupressure or acupuncture applied to Neiguan P-6 provides a treatment benefit in 60-70% of patients compared to a 30% treatment benefit with sham acupressure or sham acupuncture, implying that point location is an important determinant27. In Chinese medicine nausea and vomiting are divided into subcategories according to traditional differential diagnosis: cold vomiting (han ou), heat vomiting (ren ou), phlegm vomiting (tan ou), food accumulation vomiting (shi ji ou tu), qi vomiting (qi ou), vomiting of clear water (tu qing shui), bitter vomiting (ou ku), acid vomiting (tu suan), water counterflow (shui ni), vomiting of phlegm-drool (ou tu tan xian). It is further divided into the following categories: stomach reflux (fan wei), malign obstruction (e zu), ejection of foamy drool (tu xian mo) and nausea (e xin). Acupuncture treatment for nausea and vomiting Back to the Table of Contents Basic treatment: Neiguan P-6, Zusanli ST-36, Gongsun SP-4, Zhongwan REN-12. All nausea and vomiting is the clinical sign of Stomach qi ascending counterflow, which can arise from a variety of Stomach disorders. Each of those conditions requires a different variation of acupuncture point prescription. TCM holds that when the analysis of the condition is more accurate, the practitioner has more choices to render a safer and more effective treatment. Understanding the root cause of a condition and differentiation of branch symptoms can add both to the practitioner's arsenal of treatment tools and to insight into the prognosis of the condition ï‚· ï‚· ï‚· ï‚· Spleen-Stomach vacuity cold (pi wei xu han) Signs include reduced food intake, vomiting of un-transformed food or of clear water without acid taste that gives a sense of relief, cold limbs, fatigue, dizziness, distention and fullness after eating. Tongue: pale, soft enlarged tongue, with thin tongue coating. Pulse: forceless (mai huo da wu li), moderate (huan), fine (xi). Add to basic treatment: Dadu SP-2 or Sanyinjiao SP-6. Dual vacuity of Stomach qi and yin (wei qi yin xu) Signs include dry lips and mouth, desire for fluids, inability to drink sufficient amount of fluids, reduced food intake, dry bound stool, short voiding of scant urine, sometimes hiccup and dry retching, heart palpitations, spontaneous sweating, hot flushes. Tongue: red without coating or peeling tongue coating. Pulse: Rapid (shu), vacuous (xu), fine (xi). Add to basic treatment: Zhaohai KID-6 and or Tianshu ST-25. Liver- Stomach disharmony due to qi congestion (gan wei bu he) Signs include pain in both ribs sides, belching, oppression and fullness in the upper abdomen, stomach pain, swallowing of up-flowing acid, bloating, indigestion, poor appetite, vomiting of acid fluid or food. Tongue: normal pink or slightly purple, with moderate coating. Pulse: moderate (huan), slippery (hua). Add to basic treatment: Taichong LIV-3 and Hegu L.I.-4 or Tianshu ST-25. Phlegm-heat accumulation (tan re ji) Signs include gurgling sounds in the stomach, heart palpitations, dizzy head, ï‚· flowery vision, vomiting of phlegm with or without bitter taste, oppression and fullness in the chest. Tongue: red or purple tongue, yellow slimy tongue coating. Pulse: rapid (shu), string-like (xian). Add to basic treatment: Yanglingquan GB-34. Debilitation of the life gate fire (ming men huo shuai) Signs include bright white complexion, aversion to cold, lack of warmth in the extremities, dizziness, tinnitus, weak lower back and knees, profuse urination at night or inhibited urination, vomiting of untransformed food, weakness, lassitude of spirit, oedema. Tongue: pale enlarged tongue Pulse: fine (xi), sunken (chen). Add to basic treatment: Taixi KID-3 or Sanyinjiao SP-6. Differentiation according to clinical symptoms and signs ï‚· ï‚· ï‚· ï‚· ï‚· ï‚· Vomiting and nausea with dryness in the throat and mouth: signs include dryness in the mouth and throat, mouth sores, dry retching, thirst. Tongue: red, no coating or peeling tongue coating, cracked tongue. Pulse: rapid (shu), vacuous (xu), fine (xi). Add to basic treatment: Zhaohai KID-6. Vomiting and nausea with bitter taste: signs include bitter taste in the mouth or bitter vomiting, irritability, gurgling sounds in the stomach. Tongue: red or purple tongue, yellow slimy tongue coating, or no tongue coating. Add to basic treatment: Yanglingquan GB-34. Nausea and vomiting of untransformed food: signs include vomiting of untransformed food, sense of relief after vomiting, lack of desire to eat or drink, fatigue, fullness after eating. Tongue: pale, soft enlarged tongue, with thin tongue coating. Pulse: forceless (mai huo da wu li), moderate (huan), fine (xi). Add to basic treatment: Dadu SP-2 or Sanyinjiao SP-6. Nausea and vomiting with acid taste: signs include belching, acid foul taste in the mouth, bloating, reduced desire to eat. Add to basic treatment: Taichong LIV-3 and Hegu L.I.-4 and/or Tianshu ST-25. Vomiting of clear fluid without acid taste: signs include cold extremities, vomiting on exposure to cold or long after eating, blue-green complexion. Tongue: pale, sometimes enlarged, moist. Pulse: sunken (chen), fine (xi) pulse or sometimes string-like (xian), slow (chi). Add to basic treatment: Dadu SP-2 and or Taixi KID-3 and or Sanyinjiao SP-6. Nausea and vomiting with pain in the throat Any of the above types of nausea and vomiting with pain in the throat and neck. Add to basic treatment: Hegu L.I.-4 and Binao L.I.-14. Herbs for chemotherapy-induced nausea and vomiting Back to the Table of Contents Scientifically proven antiemetic herbs13-14 Ban Xia (Rhizoma Pinelliae Ternatae), Di Yu (Radix Sanguisorbae Officinalis), Lian Qiao (Fructus Forsythiae Suspensae), Sheng Jiang (Rhizoma Zingiberis Officinalis Recens), Wu Zhu Yu (Fructus Evodiae Rutaecarpae). Additional herbs commonly used as antiemetics Huang Lian (Rhizoma Coptidis), Shi Di (Calyx Kaki Diospyri), Zhu Ru (Caulis Bambusae in Taeniis), Ding Xiang (Flos Caryophylli), Xuan Fu Hua (Flos Inulae), Chen Xiang (Lignum Aquilaria), Zhu Ling (Sclerotium Polypori Umbellati), Dao Dou Zi (Semen Canavaliae), Gao Liang Jiang (Rhizoma Alpiniae Officinari), Rou Dou Kou (Semen Myristicae Fragranticis), Sha Ren (Fructus seu Semen Amomi), Hong Dou Kou (Fructus Galangal). Antiemetic formulas used in chemotherapy Jia Wei Ban Xia Xing Tang Ban Xia (Rhizoma Pinelliae Ternatae) 4 9, Zhu Ru (Caulis Bambusae in Taeniis) 4 9, Chen Pi (Pericarpium Citri Reticulatae) 4 9, Fu Ling (Sclerotium Poriae Cocos) 4 9, Sheng Jiang (Rhizoma Zingiberis Officinalis Recens) 4, Dang Shen (Radix Codonopsis Pilosulae) 12, Bei Sha Shen (Radix Glehniae Littoralis) 4 9, Bai Zhu (Rhizoma Atractylodis Macrocephalae) 4 9, Gan Cao (Radix Glycyrrhizae Uralensis). 3 Wen Wei Zhi Ou Tang Ban Xia (Rhizoma Pinelliae Ternatae) 4 9, Huo Xiang (Herba Agastaches seu Pogostemi) 4 9, Ding Xiang (Flos Caryophylli) 4 6, Shi Di (Calyx Kaki Diospyri) 4 6, Chen Pi (Pericarpium Citri Reticulatae) 4 9, Sheng Jiang (Rhizoma Zingiberis Officinalis Recens) 4, Gan Cao (Radix Glycyrrhizae Uralensis) 3, Da Zao (Fructus Zizyphi Jujubae) 4 6, Dang Shen (Radix Codonopsis Pilosulae) 10. Liu Wei Tong Guan Tang Xuan Fu Hua (Flos Inulae) 4 9, Dai Zhe Shi (Haematitum) 12, Fu Ling (Sclerotium Poriae Cocos) 12, Dang Shen (Radix Codonopsis Pilosulae) 15, Bai Zhu (Rhizoma Atractylodis Macrocephalae) 10, Gan Cao (Radix Glycyrrhizae Uralensis) 3, Ban Xia (Rhizoma Pinelliae Ternatae) 4 9, Chen Pi (Pericarpium Citri Reticulatae) 4 9, San Qi (Radix Pseudoginseng) (ground and taken separately) 1.5, Bei Sha Shen (Radix Glehniae Littoralis) 4 9, Ma Bin Lang (Semen Capparis) 4 6, Bai Hua She She Cao (Herba Oldenlandiae Diffusae) 24, Shu Yang Quan (Herba Solani Lyrati) 24, Wu Zhu Yu (Fructus Evodiae Rutaecarpae). 4 8 Acupuncture effects on haematologic, immunologic and hormonal function Back to the Table of Contents Decreased white blood cell (WBC) count due to chemotherapy induced myelosuppression is commonly seen in cancer patients. Studies have suggested an effect of acupuncture in the maintenance and restoration of WBC counts28-30. In a study of 48 patients with chronic leukopenia, acupuncture stimulation to Zusanli ST-36 led to an increased WBC count in over 90% of patients28. Markers of immune function, including IgG, IgA, IgM, C3 complement levels and lymphocyte reactivity to phytohemaglutinin (PHA) were alsoelevated when compared to pretreatment levels. The influence of acupuncture on specific immune function has been examined in a number of studies. A second study of 121 patients with leukopenia who were undergoing chemotherapy showed a significant increase in WBC counts following 5 days of daily acupuncture and moxibustion treatment30. In a review article, Wu et.al. summarise the immune modulatory effects of acupuncture among patients undergoing chemotherapy and radiation. These include an increase in peripheral blood counts of CD3 +, CD4 + and NK cells as well as an increase in the CD4 +/ CD8 + ratio and a decrease in secreted IL-2 receptor. In addition, macrophage activity can be elevated by both acupuncture and moxibustion31. The immune and hormonal levels of premenopausal women with benign mammary hyperplasia were compared to normal women. After acupuncture, levels of CD8 + cells rose significantly, CD4 +/ CD8 + ratio was reduced to match that of normal patients, Serum E2 and Prolactin levels were lowered and levels of FSH were increased. Over 50% of the patients had complete resolution of their nodules, while the other patients had very significant reduction. All patients responded to the acupuncture treatment and had a measurable change in immune function and endocrine effect32. Climacteric symptoms are prevalent among female cancer patients as a result of early menopause due to chemotherapy, stopping hormone replacement therapy or treatment with hormonal agents like tamoxifen. Symptoms and conditions like hot flushes, night sweats, insomnia, dry skin and vaginal dryness as well as an increase in bone mineral density loss and coronary artery disease risk, are thought to be related to waning oestrogen levels. Acupuncture has been shown in several studies to help control climacteric symptoms in over 90% of subjects.33-35 The effectiveness of acupuncture appears to be lower if the duration of symptoms has been longer. Traditional Chinese herbal therapy aimed at enhancing immune function Back to the Table of Contents Patients with cancer often demonstrate depression of immune function that usually worsens as the disease progresses. This is manifested as impaired humoral and cell-mediated responsiveness as well as decreased nonspecific defense mechanisms (e.g. natural killer, or NK cells).36 In advanced stages of breast cancer, defects in skin test responses, NK cell activity, T-cell proliferative responses to mitogens or antigens and monocyte function, along with decreases in IgG production, T-cell counts and CD4/CD8 ratios, have been noted. These immunological defects become more pronounced with progression of disease and are compounded by chemotherapy and radiotherapy. Adjuvant chemotherapy for early stage breast cancer leads to a transient drop in phytohemaglutinin (PHA) response in peripheral blood lymphocytes (PBL) at 6 months with recovery by 12 months, and in one study, a correlation between lower immune function and subsequent risk of recurrence was seen.37 However, the effect of modulating the immune system in early stage breast cancer remains unclear. An overview of trials of nonspecific immune stimulation with agents such as Bacillus Calmette-Guerin (BCG) for early stage breast cancer did not show evidence of improved outcome.38 Whether or not newer techniques of tumour specific immunostimulation such as using tumour specific antigens as immunogens, manipulating cytokines and modulating co-stimulatory pathways can be effective in advanced or early stage breast cancer is being tested in preclinical and early clinical studies. One of the intended outcomes of Chinese herbal therapy is modulation of the immune system. In one study, patients with stage III and IV stomach cancer receiving FAP (5-fluorouracil, epirubicin and cisplatin) or FMP (5-fluorouracil, mitomycin C, and cisplatin) were randomly assigned to intravenous Ren Shen (Radix Ginseng) and Mai Men Dong (Tuber Ophiopogonis Japonici) herb extract or placebo, and a significant increase in the CD4/ CD8 ratio and level of Th1 cells was seen in the treatment group along with an increase in the overall T-cell count, compared to a drop in all these indices in the control group. 39 Several herbs have been shown to have different effects on immune effector cells and cytokine levels in laboratory, animal and human studies as shown in the table, below. However, information on the influence of these therapies on recurrence and mortality in early stage breast cancer remains scant. Herbal agent Immune modulatory effects reported* Huang Qi (Radix Astragali) Increased CD4/CD8 ratio and phagocytic activity in patients with gastric cancer undergoing chemotherapy. Stimulation of lymphocyte IL-2, IL-3, IL-6, TNFa and IFN-g Dan Shen (Radix Salviae Miltiorrhizae) Increased T lymphocyte production and function Bai Zhu (Rhizoma Atractylodis Macrocephalae) Increased phagocytosis, lymphocyte transformation, rosette formation, and serum IgG post chemotherapy Fu Ling (Sclerotium Poriae Cocos) Increased monocyte GM-CSF production Enhanced recovery of myelosuppression in mice after radiation. Increased spontaneous rosette formation, lymphocyte transformation, and serum IgG Gou Qi Zi (Fructus Lycii Chinensis) Enhanced hematopoiesis, ameliorates lowering of number and function of Tlymphocytes, CTL, and NK cells in mice after cyclosphosphamide Tian Men Dong (Tuber Asparagi Cochinchinensis) Enhanced humoral and cellular immunity Wu Zhu Yu (Fructus Evodiae Rutaecarpae) Increased production of IL-1b, IL- 6, TNFa and GM-CSF in mononuclear cells in vitro Xi Yang Shen (Radix Panacis Quinquefolii) Increased TNF production, reversal of suppression of cytokine production in mice after cyclophosphamide. Increased IL-2 and IFNg by murine splenic lymphocytes both in vitro and in vivo and IL-2 and IFN-g production in mice after cyclophosphamide Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae) Increased DNA and protein synthesis in lymphocytes, IL-2 production, T- lymphocyte proliferation, and NK and CTL activity in murine splenocytes. Reduced immunosupression effect in mice caused by cyclosphosphamide and steroids Nu Zhen Zi (Fructus Ligustri Lucidi) Lessened leukopenia due to chemotherapy or radiation Liu Zhi (Radix Salix) Improved regenerative capacity of bone marrow after chemotherapy * In some cases, other herbs included in combination therapy25-26 Traditional Chinese herbs for hematopoeisis during chemotherapy Back to the Table of Contents Traditional Chinese medicine practitioners apply Fu Zheng, or supportive therapy, to benefit patients during chemotherapy. As we stated above, one aim is to restore hematopoeitic function to improve peripheral blood counts. A herbal formula used to improve leukopenia is Shi Quan Da Bu Tang (All-Inclusive Great Tonifying Decoction) which is an ancient formula first introduced during the latter Han Dynasty (25-220 C.E.). Shen et al. studied the effects of this formula on improving white blood counts in 134 patients with cancer who had previously undergone chemotherapy and radiation therapy that resulted in leukopenia. Following treatment, 113 of the 134 patients had an increase in WBC levels to normal40. In a study of 58 patients with osteogenic sarcoma undergoing chemotherapy with either cisplatin and dexamethasone (CD) or high dose methotraxate and vincristine (MV), patients receiving standard palliative care were randomly assigned to a herbal regimen or observation. In the herbal therapy arm, improvements in WBC and platelet counts were seen in the MV group and there was less transaminase enzyme elevation in the MV group. Patients in the herbal therapy arm in both chemotherapy groups also showed improvement in post therapy cardiac function (as measured by ECG reading), less nausea and vomiting and fewer skin rashes41. Herbs from the berberidaceae family can increase white blood cells. E Zhu (Rhizoma Curcumae Zedoariae) and Rou Gui (Cortex Cinnamomi Cassiae) have been shown in humans and in animals to offset the bone marrow suppressive effect of chemotherapy. Several herbs have been shown to have bone marrow stimulatory (hematopoietic) effects, including Gou Qi Zi (Fructus Lycii Chinensis), Nu Zhen Zi (Fructus Ligustri Lucidi) and Ren Shen (Radix Ginseng). The herbs Ji Xue Teng (Radix et Caulis Jixueteng) and Dang Gui (Radix Angelicae Sinensis) can also treat anaemia by increasing red blood cells13-14. Peripheral neuropathy in TCM Back to the Table of Contents The induction of peripheral neuropathy is a common factor in limiting therapy with chemotherapeutic drugs. Little is known about the mechanisms responsible for the development of neuropathy. Depending on the substance used, a pure sensory and painful neuropathy (with cisplatin, oxaliplatin, carboplatin) or a mixed sensorimotor neuropathy with or without involvement of the autonomic nervous system (with vincristine, taxol, suramin) can ensue. Neurotoxicity depends on the total cumulative dose and the type of drug used. In individual cases neuropathy can evolve even after a single drug application. A general predisposition for developing a chemotherapy-induced neuropathy has been observed in nerves previously damaged by diabetes mellitus, alcohol or inherited neuropathy. The recovery from symptoms is often incomplete and a long period of regeneration is required to restore function. Up to now, no drug is available to reliably prevent or cure chemotherapy-induced neuropathy42. In traditional Chinese medicine peripheral neuropathy was usually classified as wiltingimpediment syndrome (wei bi). As in modern medicine, it implies a vast array of disorders of the nerves and muscles. The manifestations are many and it is difficult to diagnose and treat accurately. In Chinese medicine nerves were not described in the literature until Chinese medicine was exposed to Western medicine influences. Wilting-impediment syndrome was mainly associated with the affect of various aetiologies on the channels (meridians). It was classified and described from as early as the first major medical classic, the Yellow Emperors Classic of Medicine (Neijing). Studies have reported that acupuncture can be safe and effective in improving pain and the clinical course of herpes zoster, a side effect encountered by patients undergoing chemotherapy. 43 Acupuncture has also shown a positive effect on the regeneration of nerve tissue as evidenced by improved nerve conduction in patients suffering from peripheral neuropathy44-46, 47-48. The potential to improve upon peripheral neuropathy symptoms encountered by the use of adjuvant paclitaxel (Taxol) remains unstudied. The herbs Tian Ma (Rhizoma Gastrodiae Elatae) and Du Zhong (Cortex Eucommiae Ulmoidis) show a nerve-regenerating effect in animal models . 49 The following is a traditional classification and treatment of wilting-impediment syndrome that correspond to peripheral neuropathy induced by various chemotherapeutic agents: Bone wilting (gu wei) Symptoms: limp aching lumbar spine preventing normal movement, weak atrophying lower limbs preventing the patient from getting out of bed, weak teeth and a somber dark facial complexion. Hu Qian Wan (Hidden Tiger Pill) Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae), Gui Ban (Plastrum Testudinis), Huang Bai (Cortex Phellodendri), Zhi Mu (Radix Anemarrhenae Asphodeloidis), Long Gu (Os Draconis), Suo Yang (Herba Cynomorii Songarici), Huai Niu Xi (Radix Achyranthis Bidentatae), Dang Gui (Radix Angelicae Sinensis), Bai Shao (Radix Paeoniae Lactiflorae), Chen Pi (Pericarpium Citri Reticulatae), Gan Jiang (Rhizoma Zingiberis Officinalis), Yang Rou (Lamb Meat). Jin Gang Wan (Metal Strength Pill) Sha Yuan Ji Li (Semen Astragali Complanati), Qian Shi (Semen Euryales Ferox), Lian Xu (Stamen Nelumbinis Nucifera), Su Zhi Long Gu (Crispy Fried Os Draconis), Duan Mu Li (Calcined Concha Ostreae), Lian Zi Rou (Semen Nelumbinis Nuciferae), Nu Zhen Zi (Fructus Ligustri Lucidi), Gui Ban (Plastrum Testudinis) . Flesh wilting (rou wei) Symptoms: numbness of the muscles, in severe cases inability to move the limbs. Zhi Lian Er Chen Tang (Gardenia and Coptis Two-Cured Decoction)Ban Xia (Rhizoma Pinelliae Ternatae), Chen Pi (Pericarpium Citri Reticulatae), Fu Ling (Sclerotium Poriae Cocos), Gan Cao (Radix Glycyrrhizae Uralensis), Zhi Zi (Fructus Gardeniae Jasminoidis), Huang Lian (Rhizoma Coptidis), Wu Mei (Fructus Pruni Mume). Vessel wilting (mai wei) Symptoms: the joints in the four limbs are as if they are broken, inability to lift the limbs, and weakness in the lower leg preventing the patient from standing. Si Wu Tang (Four-Substance Decoction) Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae), Dang Gui (Radix Angelicae Sinensis), Bai Shao (Radix Paeoniae Lactiflorae), Chuan Xiong (Radix Ligustici Wallichii). Damp-heat wilting (shi re wei) Symptoms: atrophy of the muscles of the limbs, slight swelling, and numbness of the lower limbs, generalised sense of heaviness, oppression in the chest, difficult dark urination. Jia Wei Er Miao San (Supplemented Two-Marvel Powder) Huang Bai (Cortex Phellodendri), Cang Zhu (Rhizoma Atractylodis), Huai Niu Xi (Radix Achyranthis Bidentatae), Yi Yi Ren (Semen Coicis Lachryma-jobi), Huang Qin (Radix Scutellariae Baicalensis). Damp phlegm wilting (shi tan wei) Symptoms: Atrophy and weakness of the limbs, lower legs and knees, fatigue. Er Cheng Tang Jia Jian (Modified Two-Cured Decoction) In addition to Er Cheng Tang: Cang Zhu (Rhizoma Atractylodis), Bai Zhu (Rhizoma Atractylodis Macrocephalae), Huang Qin (Radix Scutellariae Baicalensis), Huang Bai (Cortex Phellodendri), Zhu Li (Succus Bambusae), Jiang Zhi (Ginger juice). Dryness-heat wilting (zao re wei) Symptoms: limpness of the extremities, movement is difficult and stiff, dry skin and hair, dry mouth and parched lips. Qing Zao Jiu Fei Tang (Eliminate Dryness and Rescue the Lungs Decoction) Sang Ye (Folium Mori Albae), Shi Gao (Gypsum), Mai Men Dong (Tuber Ophiopogonis Japonici), E Jiao (Gelatinum Asini), Hei Zhi Ma (Semen Sesami Indici), Ku Xing Ren (Semen Pruni Armeniacae), Mi Zhi Pi Pa Ye (Honey-fried Folium Eriobotryae Japonicae), Ren Shen (Radix Ginseng), Gan Cao (Radix Glycyrrhizae Uralensis). Blood stasis wilting (xue yu wei) Symptoms: atrophy, limpness, and pain in the limbs, difficult movement Tao Hong Si Wu Tang (Four-Substance Decoction with Safflower and Peach Pit) Dang Gui (Radix Angelicae Sinensis), Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae), Chuan Xiong (Radix Ligustici Wallichii), Bai Shao (Radix Paeoniae Lactiflorae), Hong Hua (Flos Carthami Tinctorii), Tao Ren (Semen Persicae) . Blood impediment (xue bi) Symptoms: numbness and pain in the limbs. Dang Gui Tang (Tangkuei Decoction) Dang Gui (Radix Angelicae Sinensis), Hou Po (Cortex Magnoliae Officinalis), Gan Cao (Radix Glycyrrhizae Uralensis), Ban Xia (Rhizoma Pinelliae Ternatae), Ren Shen (Radix Ginseng), Shan Jiao (Zanthoxyli Piperati). or Huang Qi Gui Zhi Wu Wu Tang (Astragalus and Cinnamon Twig Five-Substance Decoction) Huang Qi (Radix Astragali), Gui Zhi (Ramulus Cinnamomi Cassiae), Sheng Jiang (Rhizoma Zingiberis Officinalis Recens), Bai Shao (Radix Paeoniae Lactiflorae), Da Zao. Blood vacuity impediment (xue xu bi) Symptoms: numbness of the skin and inabillity to lift the limbs. Dang Gui Jian Zhong Tang (Tangkuei Decoction to Construct the Middle) Dang Gui (Radix Angelicae Sinensis), Yi Tang (Saccharum Granorum), Gui Zhi (Ramulus Cinnamomi Cassiae), Bai Shao (Radix Paeoniae Lactiflorae), Zhi Gan Cao (Radix Glycyrrhizae Praeparatae), Sheng Jiang (Rhizoma Zingiberis Officinalis Recens), Da Zao (Fructus Zizyphi Jujubae). Qi vacuity impediment (qi xu bi) Symptoms: inhibited movement of the joints, cold body and numbness in the limbs. Si Jun Zi Tang (Four-Gentlemen Decoction) plus Fu Zi (Radix Aconiti Carmichaeli Praeparatae) and Rou Gui (Cortex Cinnamomi Cassiae). Flesh impediment (rou bi) Symptoms: pain in the muscles that may be accompanied by sweating all over the body, limp atrophied muscles, numbness of the skin and clouded spirit. Shen Xiao Huang Qi Tang (Wondrous Effect Astragalus Decoction) Huang Qi (Radix Astragali), Yi Tang (Saccharum Granorum), Gui Zhi (Ramulus Cinnamomi Cassiae), Bai Shao (Radix Paeoniae Lactiflorae), Zhi Gan Cao (Radix Glycyrrhizae Praeparatae), Sheng Jiang (Rhizoma Zingiberis Officinalis Recens), Da Zao (Fructus Zizyphi Jujubae), Jin Yin Hua (Flos Lonicerae Japonicae), Dang Gui (Radix Angelicae Sinensis). Bone impediment (gu bi) Symptoms: pain and swelling of the joints, heavy sensation of the bones, aching of the bones and bone marrow, difficulty in lifting the limbs. Wu Bi Tang (Five Impediment Decoction) plus Long Gu (Os Draconis), Du Huo (Radix Angelicae Pubescentis) at least 30g, Rou Gui (Cortex Cinnamomi Cassiae), Niu Xi (Radix Achyranthis Bidentatae), Huang Qi (Radix Astragali) and Bei Xie (Rhizoma Dioscoreae): Qiang Huo (Rhizoma et Radix Notopterygii), Du Huo (Radix Angelicae Pubescentis), Gui Zhi (Ramulus Cinnamomi Cassiae), Qin Jiao (Radix Gentianae Macrophyllae), Hai Feng Teng (Caulis Piperis), Sang Zhi (Ramulus Mori Albae), Dang Gui (Radix Angelicae Sinensis), Chuan Xiong (Radix Ligustici Wallichii), Mu Xiang (Radix Saussureae seu Vladimirae), Ru Xiang (Gummi Olibanum), Gan Cao (Radix Glycyrrhizae Uralensis), Fang Feng (Radix Ledebouriellae Sesloidis), Wei Ling Xian (Radix Clemetidis Chinensis), Cang Zhu (Rhizoma Atractylodis). Each of the above has a specific traditional aetiology, or underlying pattern, associated with it. Generally speaking the pattern is identified by determining whether it is internal or external in origin, yin or yang in nature, and whether it exhibits signs of repletion or vacuity and is characterised by wind, cold, damp or heat symptoms. The complexity of the pattern and the identification of the specific disorder create a variety of treatment principles. It is further complicated by the fact that each patient may report differences in their subjective symptoms and signs. That will create a mixture of the treatment principles that make the treatment quite individualised. In the case of iatrogenic peripheral neuropathy, caused by the use of paclitaxil (taxol) the definitions of external and internal are hard to clarify, and yin and yang can be mixed in their manifestations. Therefore, careful observation of the symptoms and signs is required. Standard acupuncture point selection Points from the standard point selection for peripheral neuropathy can be utilised at each treatment depending on the limbs and the side the neuropathy is experienced. Hegu L.I.-4, Waiguan SJ-5, Zusanli ST-36, Jiexi ST-41, Yanglingquan GB-34, Xuanzhong GB-39. Indications for additional acupuncture point selection Heat in the Lung: Chize LU-5 Damp heat: Pishu BL-20, Yinlingquan SP-9 Liver and Kidney essence vacuity: Ganshu BL-18, Shenshu BL-23 Vessel wilting impediment: Ganshu BL-18, Shenshu BL-23 Bone wilting impediment: Taixi KID-3 Flesh wilting impediment: Mingmen DU-4 Sinew wilting impediment: Taichong LIV-3 Shoulder and elbow involvement: Jianyu L.I.-15, Quchi L.I.-11 Hip involvement: Biguan ST-31, Huantiao GB-30 Addendum: The use of docetaxel (Taxotere) in early stage breast cancer Back to the Table of Contents Several clinical trials have explored the efficacy of docetaxel (Taxotere) as primary chemotherapy for breast cancer. Two large, randomised phase III trials have demonstrated significant improvements in clinical and pathologic response rates with the sequential addition of docetaxel to an anthracycline-containing preoperative regimen. A trial conducted in the United Kingdom demonstrated that docetaxel sequential to CVAP (cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin [Adriamycin], prednisolone) produced a higher overall clinical response rate (94% vs 66%, P = .001) and pathologic complete response rate (34% vs 18%) compared to additional cycles of CVAP as primary chemotherapy. This translated into a survival advantage for docetaxel-treated patients, whose 3-year disease-free and overall survival were significantly improved (97% vs 84%; 90% vs 77%, P = .03). The results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-27 demonstrated that primary doxorubicin/cyclophosphamide followed by docetaxel significantly increased the clinical complete response (65% vs 40%, P < .001) and pathologic complete response rates (25.6% vs 13.7%, P < .001) and decreased the rate of positive axillary nodes (40.5% vs 48.5%, P = .01). Final analysis of NSABP B-27 may also potentially demonstrate improved disease-free and overall survivals. Additional phase II and phase III randomised trials have compared docetaxel/anthracycline combinations with standard anthracycline-based regimens. In the BCIRG 001 trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC 5- fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients, the interim analysis after 33 months of follow up TAC shows statistically significant improvements in disease free survival (DFS) (32% risk reduction) and overall survival (OS) in patients with 1-3 positive lymph nodes (54% risk reduction). Women on this trial suffered more febrile neutropenia (24% vs. 2%) and severe infections (2.8% vs. 1.3%) with TAC. Other significant side effects to TAC were severe asthenia (11%) and stomatitis (7%). Final analysis will be available in three years when 5 years of follow up will be concluded. Due to the fact that the interim analysis shows such promising benefit at this time many oncologists offer TAC to women with even earlier disease. Unfortunately jumping to such conclusions may prove ineffective especially in lieu of the excitement paclitaxel (taxol) created in its early adjuvant trials of the mid 1990's.50-52 Taxotere can cause severe bone marrow suppression in women with breast cancer (neutropenia 98.5%, leukopenia 98.6%, thrombocytopenia 9.2%, anemia 93.6% and febrile neutropenia 12.3%). It can also cause hypersensitivity reactions (any 17.6%, severe 2.6%) with flushing, localised skin irritations and acute fluid retention. Generally patients are premedicated with the corticosteroid dexamethazone (decadron) in order to prevent severe hypersensitivity events. Fluid retention occurs in 59.7% of women, neuropathy in 58.3%, skin irritations in 47%, stomatitis in 51.7%, hair loss in 74.2%, fatigue in 66.3% muscular pain in 21.1%, joint pain in 8.2%, nausea in 42%, vomiting in 23.4%, diarrhoea in 42.6%53. The caveat with diarrhea or abdominal pain with women undergoing taxotere chemotherapy is that they may develop severe colitis with possible bowel perforation. This symptom should be taken seriously if encountered.54 Various TCM treatments can help prevent and treat many of the above symptoms. The difficulty is addressing all the possible symptoms at once. From a TCM point of view taxotere seems to damage the jing and yin fluids, causing severe bone marrow suppression with deficient heat symptoms and possible acute separation of yin and yang causing hypersensitivity reaction, severe oedema, bowel perforation and septic death (1.4%). The inclusion in the Formula during Taxotere chemotherapy of the heat clearing herbs Pu Gong Ying (Herba Taraxaci Mongolici cum Radice), Jin Yin Hua (Flos Lonicerae Japonicae) and Sheng Di Huang (Radix Rehmanniae Glutinosae), as well as the increased dose of He Shou Wu (Radix Polygoni Multiflori), is to address these possible dangers. In older women Bie Jia (Carapax Amydae Sinensis) and Bai Hua She She Cao (Herba Oldenlandiae Diffusae) can be considered as well. Bu Gu Zhi (Fructus Psoraleae Corylifoliae) is very significant in this formula since it can reduce hypersensitivity reactions as well as prevent neuropathy and myalgias. Stomatitis Symptom: heat, pain, increased flow of saliva, bad breath (rancid smell usually), restlessness, sometimes fever, loss of appetite. Rinse mouth with Green tea (3 grams) + Jin Yin Hua (Flos Lonicerae Japonicae) (10 grams). Steep with boiling water for 3-5 minutes. An alternative to this rinse is Xuan Shen (Radix Scrophulariae Ningpoensis) (10 grams) prepared and administered in the same way. Skin Rashes Add to the main formula: Sheng Di Huang (Radix Rehmanniae Glutinosae) increase to 30- 60 grams Shan Zhu Yu (Fructus Corni Officinalis) Mu Dan Pi (Cortex Moutan Radicis) Rou Cong Rong (Herba Cistanches) Although messy an external wash can be prepared with: Ku Shen (Radix Sophorae Flavescentis) 30 grams Huang Bai (Cortex Phellodendri) 30 Bai Xian Pi (Cortex Dictamni Dasycarpi Radicis) 15 Boil with 4 cups of water for 60 minutes and apply to affected areas with a wet gauze for 60 minutes. Conclusion Back to the Table of Contents From the limited scientific research and empirical evidence, TCM therapies hold the potential to play an important role in ameliorating the many toxic side effects of chemotherapy and radiation for early stage breast cancer as well as in improving long term outcome. Very sparse and conflicting data currently exists on the mechanisms and clinical benefits of these therapies. Moreover, the practice of TCM modalities is highly individualised rather than standardised. The current literature reflects the heterogeneity of the therapies studied, and conclusions are usually limited by inadequately described outcome measures and statistical methods. Nevertheless, these approaches enjoy tremendous interest and use worldwide given their historical and natural appeal. The lay press, media, and even many books and articles aimed at women with breast cancer provide extensive coverage of these modalities and even recommendations for their use, yet there has been very little dissemination of scientific critiques of these therapies. This may be due to a commonly held belief that TCM modalities are not amenable to the same types of analytical studies inthe laboratory and clinic that are reserved for biomedical innovations. Though the practice of TCM has been modified over time, some empirically derived observations may be clinically useful, even if the physiologic basis remains unclear. We hypothesise that certain traditional Chinese medical disease categories may in fact relate to modern molecular and cellular biology classifications. Just as necessary vitamins and cofactors are derived from plants, so possibly are substances that may be useful in certain disease states. Furthermore, it is plausible that in some cases, the biological effects of herbs in higher organisms require several components whose presence in the plant may have evolved over time. There are examples of biological activity of herbal extracts that cannot be replicated with any single pure compound isolated and purified from the extract. On the other hand, many modern drugs originated from single plantderived molecules. In order to validate the usefulness of TCM for women with breast cancer, there is a need for safety and feasibility studies followed by controlled studies with well defined and clinically relevant endpoints and with adequate statistical power. Given its purported activities in symptom control, immunological effects and anti-tumour activity, TCM is an attractive modality to study in the adjuvant setting. Several difficulties remain in conducting such trials, however. A method for prioritising agents for study needs further refinement given the discordance in the literature and the numerous herbs used. In some cases, it may be difficult to separately evaluate modalities that are commonly used together - for example, herbal agents and acupuncture. Assessing safety may be difficult in patients receiving chemotherapy or in those with other co-morbid problems. Innovations in trial design such as cross-over schemes or 2:1 randomisations may improve accrual. Interpreting data from pilot trials is difficult because of weaker conclusions from multiple datapoint and other exploratory analyses. The ultimate demonstration of benefit will require large randomised studies, and so far, few funding mechanisms exist for such large-scale trials. Formularies for Traditional Chinese Medicine in the Treatment of Breast Cancer Formula for AC Chemotherapy Back to the Table of Contents Herb (name) Dose (grams) Huang Qi (Radix Astragali) 30 Dan Shen (Radix Salviae Miltiorrhizae) 15 Bai Zhu (Rhizoma Atractylodis Macrocephalae) 12 Fu Ling (Sclerotium Poriae Cocos) 15 Ze Xie (Rhizoma Alismatis Plantago-aquaticae) 10 Gou Qi Zi (Fructus Lycii Chinensis) 15 Huang Jing (Rhizoma Polygonati) 15 Tian Men Dong (Tuber Asparagi Cochinchinensis) 12 Mai Men Dong (Tuber Ophiopogonis Japonici) 12 Ji Xue Teng (Radix et Caulis Jixueteng) 20 He Shou Wu (Radix Polygoni Multiflori) 12 Bei Sha Shen (Radix Glehniae Littoralis) 15 Sheng Jiang (Rhizoma Zingiberis Officinalis Recens) 10 Ban Xia (Rhizoma Pinelliae Ternatae) 10 Wu Zhu Yu (Fructus Evodiae Rutaecarpae) 15 Shi Di (Calyx Kaki Diospyri) 20 Xi Yang Shen (Radix Panacis Quinquefolii) 12 Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae) 12 Nu Zhen Zi (Fructus Ligustri Lucidi) 15 Qian Shi (Semen Euryales Ferox) 10 Formula for CMF Chemotherapy (to be taken throughout the treatment and modified according to symptoms) Back to the Table of Contents Herb (name) Dose (grams) Huang Qi (Radix Astragali) 30 Dang Shen (Radix Codonopsis Pilosulae) 12 Bai Zhu (Rhizoma Atractylodis Macrocephalae) 10 Fu Ling (Sclerotium Poriae Cocos) 10 Ze Xie (Rhizoma Alismatis Plantago-aquaticae) 10 Gou Qi Zi (Fructus Lycii Chinensis) 15 Huang Jing (Rhizoma Polygonati) 15 Mai Men Dong (Tuber Ophiopogonis Japonici) 10 Ji Xue Teng (Radix et Caulis Jixueteng) 20 He Shou Wu (Radix Polygoni Multiflori) 10 Bei Sha Shen (Radix Glehniae Littoralis) 15 Sheng Jiang (Rhizoma Zingiberis Officinalis Recens) 8 Ban Xia (Rhizoma Pinelliae Ternatae) 10 Wu Zhu Yu (Fructus Evodiae Rutaecarpae) 10 Shi Di (Calyx Kaki Diospyri) 10 Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae) 12 Nu Zhen Zi (Fructus Ligustri Lucidi) 15 Qian Shi (Semen Euryales Ferox) 10 Yu Jin (Tuber Curcumae) 10 Wu Yao (Radix Linderae Strychnifoliae) 10 Formula During Taxol Chemotherapy (to be taken throughout the treatment and modified according to symptoms) Back to the Table of Contents Herb (name) Dose (grams) Huang Qi (Radix Astragali) 30 Dang Shen (Radix Codonopsis Pilosulae) 12 Bu Gu Zhi (Fructus Psoraleae Corylifoliae) 15 Gu Sui Bu (Rhizoma Gusuibu) 15 Chuan Xiong (Radix Ligustici Wallichii) 15 Dan Shen (Radix Salviae Miltiorrhizae) 15 Nu Zhen Zi (Fructus Ligustri Lucidi) 15 Ji Xue Teng (Radix et Caulis Jixueteng) 30 He Shou Wu (Radix Polygoni Multiflori) 10 Gou Qi Zi (Fructus Lycii Chinensis) 15 Huang Jing (Rhizoma Polygonati) 15 Tai Zi Shen (Radix Pseudostellariae Heterophyllae) 12 Fu Ling (Sclerotium Poriae Cocos) 10 Ze Xie (Rhizoma Alismatis Plantago-aquaticae) 10 Bei Sha Shen (Radix Glehniae Littoralis) 15 Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae) 12 Bai Zhu (Rhizoma Atractylodis Macrocephalae) 10 Chun Gen Bai Pi (Cortex Ailanthi Altissimae) 15 Formula During Taxotere Chemotherapy (to be taken throughout the treatment and modified according to symptoms) Back to the Table of Contents Herb (name) Dose (grams) Huang Qi (Radix Astragali) 30 Dang Shen (Radix Codonopsis Pilosulae) 12 Chuan Xiong (Radix Ligustici Wallichii) 15 Dan Shen (Radix Salviae Miltiorrhizae) 15 Nu Zhen Zi (Fructus Ligustri Lucidi) 15 Ji Xue Deng Xin Cao (Medulla Junci Effusi) 30 He Shou Wu (Radix Polygoni Multiflori) 15 Gou Qi Zi (Fructus Lycii Chinensis) 15 Huang Jing (Rhizoma Polygonati) 15 Fu Ling (Sclerotium Poriae Cocos) 10 Ze Xie (Rhizoma Alismatis Plantago-aquaticae) 10 Bei Sha Shen (Radix Glehniae Littoralis) 15 Sheng Di Huang (Radix Rehmanniae Glutinosae) 12 Bai Zhu (Rhizoma Atractylodis Macrocephalae) 10 Chun Gen Bai Pi (Cortex Ailanthi Altissimae) 15 Pu Gong Ying (Herba Taraxaci Mongolici cum Radice) 20 Jin Yin Hua (Flos Lonicerae Japonicae) 15 Bu Gu Zhi (Fructus Psoraleae Corylifoliae) 10 Tables and Studies - Traditional Chinese Medicine in the Treatment of Breast Cancer Table1: Commonly Prescribed Herbs for Prevention of Breast Cancer Back to the Table of Contents Pinyin name Chai Hu Botanical name and family Traditional indications Radix Bupleurum chinensis DC. (Umbelliferae) Reducing fever, soothing the liver and upper GI, cures organ ptosis. Modern research CNS effects (antipyretic effect, sedative effect, analgesic and antitussive effect.) Anti-inflammatory effect. GI effect Chemical constituents Triterpene saponins: saikosaponins a, b1- b4, c, d, e and f. Essential oils: bupleurmol, spinasterol, stigmasterol (hepato-protective and choleretic effect, prevents gastric ulcer. Hypolipemic effect. Antimicrobial effect, protects from renal damage. Dang Gui Radix Angelica sinensis (Oliv.) Diels (Umbelliferae) Enriching the blood and activating blood circulation. Regulating menstruation and relieving menstrual pain. Used for constipation. Different fractions can both inhibit and stimulate uterine contractions. Endometrial proliferation without direct oestrogenic effect was found. Decreases contraction magnitude and frequency of heart muscle. Significantly dilates and increases coronary flow. Decreases artery pressure while reducing arterial resistance and increasing arterial flow. Inhibits platelet aggregation and serotonin release. Decreases blood lipids and reduces arteriosclerosis. Analgesic effect. Antiasthmatic effect. Essential oils: ligustilide, ferulic acid, n-butyli-denephthalide, nvalero- phenone-Ocarboxylic acid. Novolatile: brefeldin A, sitosterol, stigmasterol, sitosterol-D-glucoside, vitamin A, B12 and E. Bai Shao Radix Paeonia lactiflora Pall. (Ranunculaceae) Supplements blood, controls pain, alleviates sudden onset of disease, subdues hyperactive liver, controls excessive sweating. Antispasmodic and analgesic effect by lowering muscle tonicity. Sedative effect, inhibits gastric secretions and inhibits gastric ulceration. Antibacterial effect. Protects from myocardial ischemia and from platelet Paeoniflorin, paeonol, paeonin, albiflorin, oxypaeoniflorin, benzoylpaeoniflorin and paeoniflorigenone. Benzoic acid, sitosterol, gallotannin, pedunculagin. Polysaccharide: peonan SA. Acidic polysaccharide: peonan Chen Pi Pericarpium Regulating the Citrus reticulata flow of qi and blanco (Rutaceae) invigorating digestive function. Eliminating damp and resolving phlegm. Inhibits GI smooth muscle movement. Wang Semen Vaccariae Bu Liu pyramidata Xing Medic. (Caryophyllacea) Moves blood, regulates menses, increases lactation, disperses swelling carbuncles, promotes healing of incised wounds. aggregation. Causes coronary and peripheral vasodialation. SB, peonan PA and Triterpenoids. Inhibits gastric ulceration without inhibition of gastric secretions. Expectorant and antitussive effect. Anti-inflammatory and antiallergic effect. Relaxes uterine muscle contraction. Essential oil: dlimonene, citrol. Monoterpenes: pinene, pinene, camphene, myrcene, 3-carene, phellandrene, phellandrene, terpinene. Flavones, alkaloids, synephrine and Nmethyltyramine. Stimulates uterine contraction. Saponins: vacasegoside, isosaponarin. Starch, fat, alkaloids, cyclic peptides. Table2: Formulas Commonly Used in the Trials Back to the Table of Contents Formula Name TCM Differentiation Dan Zhi Xiao Yao San (Moutan and Gardenia Rambling Powder) plus Yi Huang Tang (Change Yellow Discharge Decoction) plus San Miao Liver qi depression with San (Three Wonders Powder ) with Xiang Fu (Rhizoma Cypery damp heat pattern rotundi) Dan Zhi Xiao Yao San (Moutan and Gardenia Rambling Powder) plus Tao Hong Si Wu Tang (Persica and Carthamus Four Materials Liver qi depression with Decoction) plus Qing Pi (Pericarpium Citri reticulatae viridis), Yan blood stasis pattern Hu Suo (Rhizoma Corydalis) and Yu Jin (Rhizoma Curcuma) Dan Shen Gui Pi Tang (Salvia Restore the Spleen Decoction) plus Xiang Fu (Rhizoma Cyperi rotundi) and Yu Jin (Rhizoma Curcuma) Liver qi depression with heart/ spleen vacuity pattern Table 3: Formulas Used in Sixth Breast Cancer Prevention Trial Back to the Table of Contents 1. For Liver QI Depression and Binding Pattern 2. For Irregularity of the Chong and Ren Pattern Chai Hu (Radix Bupleuri) Shu Di Huang (Radix Rehmanniae Glutinosae Conquitae) Dang Gui (Radix Angelica Sinensis) Shan Yao (Radix Dioscoreae Oppositae) Chi Shao (Radix Paeoniae Rubrae) Gou Qi Zi (Fructus Lycii Chinensis) Bai Shao (Radix Paeoniae Lactiflorae) Shan Zhu Yu (Fructus Corni Officinalis) Tao Ren (Semen Persicae) Lu Jiao Jiao (Colla Cornu Cervi) Hong Hua (Flos Carthami Tinctorii) Tu Si Zi (Semen Cuscutae) Dan Shen (Radix Salviae Miltiorrhizae) Xia Ku Cao (Spica Prunellae Vulgaris) Xiang Fu (Rhizoma Cyperi Rotundi) Hai Zao (Herba Sargassii) Xia Ku Cao (Spica Prunellae Vulgaris) Kun Bu (Thallus Algae) Lian Qiao (Fructus Forsythiae Suspensae) Hong Hua (Flos Carthami Tinctorii) Chuan Lian Zi (Fructus Meliae Toosendan) Bai Shao (Radix Paeoniae Lactiflorae) Gua Lou Ren (Semen Trichosanthis) Chen Pi (Pericarpium Citri Reticulatae) Yan Hu Suo (Rhizoma Corydalis Yanhusuo) Chuan Sha Jia (Squama Manitis Pentadactylae) Ban Xia (Rhizoma Pinelliae Ternatae) Hai Zao (Herba Sargassii) Kun Bu (Thallus Algae) The herbs were made into capsules and given 6 capsules 3 times a day for formula 1, and 4 capsules 3 times a day for formula 2. Table 4: Herbs Commonly Prescribed with Chemotherapy, and Chinese Anticancer Agents Back to the Table of Contents Botanical name and family Traditional indications Huang Qi Radix Astragalus membranaceus (Fisch.) Bge. (Leguminosae) Supplements qi, increases yang, consolidates the surface, increases resistance to disease, controls sweating, delivers fluids, disperses swelling, discharges pus. Increased CD4/CD8 ratio and phagocytic activity in patients with gastric cancer undergoing chemotherapy. Stimulation of lymphocyte IL-2, IL-3, IL-6, TNFa and IFN-g. Diuretic effect and antinephrotoxic effect. Antiinflammatory effect. Hepatoprotective effect. Saponins: astragalosides I-VIII, acetylastragaloside I. Flavones: kaempferol, quercitin, isorhamnetin, rhamnocitin, formononetin, calycosin. Polysaccharides: astragalans I,II,III. Glucans: AG-1 and AG- 2. Bai Zhu Rhizoma Atractylodis macrocephalae Koidz. (Compositae) Replenishes qi and reinforces the spleen. Harmonises the spleen and stomach, relieves fatigue. Induces diuresis and eliminates damp. Arrests excessive perspiration and spontaneous Increased phagocytosis, lymphocyte transformation, rosette formation, and serum IgG post chemotherapy. Increases body weight and endurance. Potentiates reticuloendothelial system. Diuretic effect, antiulcerative effect, Essential oil:s atractylon. Lactones: atractylenolides II,III. Vitamin A. Sesquiterpene and furfural. Pinyin name Modern research Chemical Constituents sweating. hypoglycaemic effect. Anticoagulant effect. Hepatoprotective effect. Lowers blood pressure and dialates blood vessels. Ling Zhi Ganoderma lucidum (Leyss. Ex Fr.) Karst. (Basidiomycetes) Nourishes, tonifies, supplements qi and blood. Removes toxins, astringes essence and disperses accumulation. Relieves fatigue and subdues deficiency insomnia. Antitussive effect. Expectorant effect. Hypotensive effect. Hepatoprotective effect. Antibacterial effect. Sensitises radiation effect. Protects from radiation damage. Immune stimulating effect. Ergosterol, coumarin, mannitol, polysaccharides, organic acids, resins. Dang Shen Radix Codonopsis pilosula (Franch.) Nannf. (Campanulaceae) Tonifies qi, increases body resistance, promotes digestion & absorption of nutrients. Increases secretion of body fluids. Promotes digestion and metabolism. Stimulates the CNS: decreases monoxidase-B (MAO-B) activity in the brain. Hematopeiteic. Hypotensive effect. Significantly decreases erythrocyte electrophoretic time and fibrinogen. Enhances cardiac function and increases tolerance to cold Phytosterols and triterpenes: spinasterol and Dglucopyranoside, 7-stigmasterol, 5,22stigmasterol, taraxerol, taraxeryl acetate and friedelin. Phenols: syringaldehyde, vanillic acid, syringin, tangshenoside I. Essential oils: methyl palmitate, octadecane, nonadecane, heptadecane, carboxylic acid. without increasing body weight and it elevates activity of superoxide dismutase (SOD). Increases phagocytosis. Promotes leukocyte production. Increases haemoglobin levels, antagonises insulin induced hypoglycaemia, but was ineffective with phagocytosis and the transformation of lymphocytes. It also inhibited type II allergic reactions and stimulated the adrenal cortex Inhibits transplanted sarcoma 180 in mice. Fu Ling Sclerotium Poria cocos (Schw.) Wolf (Polyporaceae) Induces diuresis and excretes dampness. Invigorates the spleen function. Tranquillises the mind. Increased monocyte GMCSF production Enhanced recovery of myelosuppression in mice after radiation. Increased spontaneous rosette formation, lymphocyte transformation, and serum IgG. Diuretic effect. Sedative effect. Antitumour Polysaccharide: pachyman. Triterpene: pachymic acid, tumulosic acid, eburicoic acid, pinicolic acid. promotion effect. Increases cardiac contractility. Antineoplastic agents Pu Gong Ying Herba Taraxacum mongolicum Hand.- Mazz. (Compositae) Removes toxic heat. Removes swelling and nodulation. Relieves dysuria. Antimicrobial effect. Immune stimulating effect: increases peripheral lymphoblast transformation rate. Choloretic effect and hepatoprotective effect. Taraxasterol, taraxacerin, taraxicin, choline, inulin and pectins. Jin Yin Hua Flos Lonicera japonica Thunb. (Caprifoliaceae) Removes toxic heat. Dispels wind heat. Antimicrobial effect. Antiinflammatory effect, antilipaemic effect. Decreases pregnancy rate after mating. Antispasmodic effect. Diuretic effect. Chlorogenic acid. Inositol and flavonone. Essential oils: 2,6,6trimethyl-2-vinyl-5hydroxytetrahydropyran and linalool. Shan Ci Gu Bulbus Cremastra variabilis (Blume) Nakai (Orichidaceae) Reduces heat. Removes toxins, disperses accumulation, dissipates swelling. Antineoplastic Tulipine, colchicines. effect. Cardiotonic effect. Antiviral effect. Huang Yao Zi Rhizoma Dioscorea bulbifera L. (Dioscoreaceae) Resolves phlegm. Controls cough. Disperses goitre and controls bleeding. Antibacterial effect. Antifungal effect. Increases uterine contraction. Terpenoids: diosbulbin A,B,C,D. 2,4,6,7tetrahydroxy-9,10dihydrophenanthrene, 2,4,5,6- tetrahydroxyphenanthrene. Tannin. Bai Hua She She Cao Herba Oldenladia diffusa (Willd.) Roxb. (Rubiaceae) Removes toxic damp heat, clears abscesses, infections with fever. Increases phagocytosis, lowers fever, arrests growth of spermatogonia and empties convoluted seminiferoous tubules. Iridoid glycosides: oldenlandosides Aand B. hentriacontane, stigmasterol, ursolic acid, oleanolic acid, b sitosterol, sitosterolDglucoside, p-coumaric acid and flavonoid glycosides. Table 5: Histology and Chinese Medical Syndrome Classification Back to the Table of Contents Chinese Medical Differentiation Type Classification Invasive Non-Invasive Stage Sim; Ad Sc Med Ecz DCIS LCIS Liver Spleen Stasis Def 1 16 19 2 2 1 37 7 40 22 4 II 21 22 3 2 6 37 33 1 1 III 15 21 2 17 15 2 19 IV 22 18 8 11 2 19 Total 74 80 7 4 7 37 7 102 81 9 24 % 34.3 37.0 3.2 1.9 3.2 47.3 37.5 4.2 11.1 Sim= Carcinoma; Ad=Adenocarcinoma; Sc= Scirrhous; Med= Medullary carcinoma; Ecz= Eczematoid cancer; DCIS= Presence of Ductal Carcinoma In-situ; LCIS= Lobular Carcinoma In-situ; Liver= Liver Stagnation (Depression) Qi Stagnation Type; Spleen= Spleen Deficiency with Phlegm and Damp Type; Stasis= Stasis and Toxin Type; Def= Blood and Qi Deficiency Type Table 6: Five Year Survival Rates for 216 Cases of Breast Cancer Back to the Table of Contents Stage Total N of survivors % of survivors N of Deaths % of Deaths I+ DCIS, LCIS 66 65 98.5 1/td> 1.5 II 72 71 98.6 1 1.4 III 38 30 78.9 8 21.1 IV 40 4 10.0 36 90.0 Total 216 170 78.7 46 21.3 Table 7: Relationship Between Five Year Survival Rates and Age Back to the Table of Contents Age Under 30 31-40 41-50 51-60 Over 60 Survivors 170 2 13 95 47 13 Deaths 46 0 6 16 17 7 Total 216 2 19 111 64 20 Of the 216 patients, 8 received Chinese herbal medicine as sole therapy; the remaining patients received a combination of TCM and WM treatment. The herbs were administered daily from between 5 years and 3 months to 17 years. Between 1970-1980 CMF (Cyclophosphamide, Methotraxate and 5-Fluorouracil) chemotherapy was used and since 1980 adriamycin or mitoxanthrone replaced cyclophosphomide. The dose and schedule of chemotherapy were similar to common oncological practice. The overall 5 year survival rate was 78.7% (170/216) for all stages. The 5-year survival rate was related to age and histological classification as follows. The highest percentage of 5-year survivors (86%) was in the 41-50 year old population (see tables 6 & 7). In terms of histological classification, highest survival rates were observed in patients with adenocarcinoma (91.3%). An analysis of the TCM classifications reveals that prognosis varies according to traditional pattern differentiation with qi and blood deficiency type being the worst prognosis (see table 8). Table 8: Relationship Between Five Year Survival Rates and Pattern Differentiation in Chinese Medicine for 216 Cases of Breast Cancer Back to the Table of Contents Results of Follow-up Survey Number Liver depression and Qi Stagnation Type Spleen Deficiency with Phlegm and Damp Type Stasis and Toxin Type Qi and Blood Deficiency Type Surviving 170 87 (85.3%) 73 (90.1%) 5 (55.6% 5 (20.8%) Deaths 46 15 (14.7%) 8 (9.9%) 4 (44.4%) 19 (79.2%) Total 216 102 81 9 24 Table 9: Fact Protocol Kang Lai Te Comparative Ratios of Treatment Effectiveness for Breast Cancer Back to the Table of Contents CR PR NR CR+PR (%) of CR+PR Experimental Group 4 6 5 10 (66.7) Control Group .2 6 9 8 (47.1) CR- complete remission; PR- partial remission (>50% of tumor load reduction); NR- No response (<50% of tumor load reduction) Based on the TNM (tumour-node-metastasis) classification, 16 cases were stage two, 48 cases were stage three, 12 cases were stage four, and one case was not classified due to incomplete records. The diagnoses were all confirmed by clinical histological and pathological tests. All of the subjects chosen for Teng Huang (Resina Garciniae) met one of the following criteria: i. did not receive prior therapy, ii. the cancer progressed on prior therapy, or, iii. had metastatic recurrence after treatment. Teng Huang (Resina Garciniae) preparations were provided by the Jiang Xi Medicinal Processing Plant. Intravenous preparations contained 100 mg. One dose equalled 100-200 mg of Teng Huang in a 5% glucose solution. A 500 ml intravenous drip was administered to the patient twice per week and 60-90 mg were administered orally (30mg pills) 2 to 3 times per day. A soft plaster containing 5% concentration of Teng Huang was applied topically to the breast tumours and changed 2-3 times per week. In general, the subjects received the herbal preparations before surgery. One month constituted one treatment cycle. After one or two treatment cycles, surgery was performed. Those for whom surgery was contraindicated, and those who refused surgical treatment, could complete multiple treatment cycles. Based on standard evaluation of tumour response, the results were as follows: markedly effective (tumour shrinkage greater than50%):15 cases (19.4%); effective (tumour shrinkage less than 50%): 44 cases (57.1%); ineffective (no change or increase in tumour size): 18 cases (23.3%). The overall effectiveness rate was 76.60%. The rate for marked effectiveness was 19.5%. For all groups the period of effective remission was between 3 to 18 months (no median is provided). During the course of treatment no bone marrow suppression was observed, and no cardiac, hepatic or renal toxicities observed. However, leakage from the intravenous drip caused soft tissue oedema. This was avoided by ensuring that there was no leak. Study 1 Back to the Table of Contents 76 women diagnosed with breast cancer were treated post surgically with herbal medicine in addition to chemotherapy and radiation. Herbal treatment was given once daily for two to eight years. The age range was 33-76 years, with 80% of the women aged 45-65. According to cancer staging, 22 were diagnosed stage I, 48 stage II, and 6 stage III. Of the 76 women who entered the trial, 8 dropped out and the remaining 68 were evaluated, providing an 89% follow-up. The duration of observation was 2-8 years. All patients were able to complete their therapy; 28 women resumed work and the rest were able to manage their daily life. Among the 68 cases, 3 women (4.4%) had recurrence of disease during the follow-up time period and two of these died during the study. Overall survival was 97.1% and overall disease free survival was 95.6%. Unfortunately, the researchers do not report tumour size, the nodal status, ER status, median follow-up, 5 year analysis, the stage of the women who recurred and description of the type and dose of chemotherapy and radiation used in the trial.55 Study 2 Back to the Table of Contents A retrospective study evaluating the clinical outcome of 216 cases of breast cancer treated with integrated TCM and WM from 1970-1988 was conducted at Guang An Men Hospital in Beijing.56 211/216 (97.7%) patients were women and 5/ 216 (2.3%) were men. The subjects ranged in age from 28-73; 175 (81.0%) were 41-60 years of age. The stage distribution was DCIS + LCIS: 44 (20.3%), stage I: 22 (10.1%), stage II: 72 (33.3%), stage III: 38 (17.6%), stage IV: 40 (18.5%) (see table 5). Study 3 Back to the Table of Contents In a randomised controlled neoadjuvant trial, 32 patients with breast cancer were treated with a combination of FACT (5-FU, Adriamycin, Cyclophosphamide and tamoxifen) and Kang Lai Te Injection or FACT alone. 57 Kang Lai Te (KLT) is a lipid emulsion from the seed of wild barley (semen Coix lacryma-jobi L. var. ma-yuen (Roman.) Stapf (Gramineae). The ingredients in the seed that show anticancer activity are composed of four free fatty acids. 58 KLT has been shown to reverse adriamycin resistance in cell cultures.59 KLT is currently in clinical trials in the US in the treatment of Non Small Cell Lung Cancer (NSCLC). The women in the trial were 27-66 years of age with an average age of 52. All patients had a Fine Needle Aspirate (FNA) to confirm diagnosis. All patients had Karnofsky scores above 80% (a performance scale for rating a persons usual activities; used to evaluate a patients progress after a therapeutic procedure). A total of 18 patients were ER positive and 14 were ER negative. 3 patients were diagnosed stage I + DCIS, 5 at stage Iia, 8 at stage Iib and 16 at stage IIIa. The treatment protocols for the two groups were as follows. The experimental group received Cytoxan 800 mg and Adriamycin 50 mg IV on the first day. 5-Fu was administered as an intravenous drip (for a minimum of six hours) daily for 5 days. A 200 ml dose of Kang Lai Te injection was administered by intravenous drip, once per day, for 10 days. A total of 20 mg of tamoxifen was given twice a day for pre-menopausal women and 10 mg of tamoxifen twice a day was prescribed for post-menopausal women. In accordance with standard treatment protocol, Metoclopromide and Dexamethasone were prescribed prior to treatment to reduce nausea and vomiting. Due to the possible side effects of phlebitis from Kang Lai Te intravenous drip, the drip was inserted into the subclavicular vein. The control group did not receive Kang Lai Te, but all other medications were similar for both groups. The patients received two cycles of treatment. The tumour was measured using double diameter area measurement. Ultrasound measurements were recorded before treatment and one week after both cycles of treatment were completed. The overall effective rate for all 32 cases was 56.2% (complete remission and partial remission (>50%) of the tumors). The experimental group had an effect rate of 66.7%, with complete remission (CR) of 26.7%. The control group had an effect rate of 47.1%, with a CR of 11.8% (see table 9). No tumour progression was observed in either group. Surgical excision was performed approximately two weeks after two cycles of chemotherapy were completed. All surgical margins were clear. Subjects in both groups experienced grade I and grade II bone marrow toxicity (primarily lowered WBC) and gastrointestinal toxicity. With supportive therapy, blood counts returned to normal and the GI distress was relieved. Toxicity experienced during the trial did not influence the administration of the second cycle of chemotherapy or the timely performance of surgery. In the experimental group, 86.7% of subjects had stable or improved Karnofsky scores. This was markedly better than the 52.9% in the control group. Study 4 Back to the Table of Contents Many herbs have been tested in China for their anticancer activity in the past decades, and several drugs currently in use or in clinical trials were developed from the herbs60. In-vitro antiproliferative assays on a panel of breast cancer cell lines treated with Chinese herbs traditionally used for breast cancer revealed that a high proportion of the herbs tested were highly active in vitro61. A clinical trial evaluating the anti-cancer effect of a single herb was conducted at Jiang Xi Province. The study included 77 women with breast cancer62. All 77 subjects were females between the ages of 20 and 86. The average age was 41.7. Study 5 Back to the Table of Contents Another study of locally advanced and metastatic breast cancer was conducted on 14 women63. All subjects were premenopausal women between 34-52 years of age (average 43 years). All subjects underwent pathological confirmation of diagnosis. Based on 1978 UICC staging: T2 N3 M0: 4 cases; T3 N3 M0: 3 cases; T 4 N3 M0: 3 cases; T3 N3 M1b: 2 cases; T4 N3 M1b: 2 cases. There was one case of bilateral breast cancer with bilateral axillary and subclavicular lymph nodes metastasis. There were also five cases of ulcerated tumours that were developing severe fungal infection. All of these patients were receiving treatment for the first time, as follows: All 14 subjects first received 2 cycles of CMF chemotherapy. After the second cycle of chemotherapy was finished, Co staged fractional radiotherapy was administered. After conclusion of the first stage of radiotherapy, a cycle of CMF was administered. This was followed by radiation boost administered with direct fields to breast, subclavicular, and axillary nodes. In between radiotherapy and chemotherapy a Chinese herbal formula was administered daily. The formula above constituted one dose. One dose was administered daily five days per week, until the end of the final stage of radiotherapy. After undergoing two cycles of chemotherapy, tumour size in the 14 subjects was reduced as follows: 50% reduction: 1 case (7.2%); 25% reduction: 6 cases (42.8%); No change: 7 cases (50%). After radiotherapy, tumours were completely eliminated in 13 subjects (92.8%). Only one subject (7.2%) had residual tumour mass who then underwent a radical mastectomy three weeks later. During the treatment period, four subjects (28.5%) had mild bone marrow suppression. For these four subjects, the dosage of the Chinese herbs was increased from five to seven doses per week and leucogen (CGSF) was also administered. After treatment, all four improved. One subject developed pneumonitis nine days after radiotherapy and was treated with steroids and antibiotics. She completely recovered after this treatment. Survival Rates: One year, three year, and five year rates were as follows: 85.7% (12/14); 50% (7/14); 35.7% (5/14). One subject had a local recurrence six months after treatment and subsequently underwent radical mastectomy and two cycles of CAF chemotherapy. Today, seven years later, she is still alive. Clinical Staging and Survival Rates: For Stage 3 breast cancer (10 subjects) the five-year survival rate was 50%. For Stage 4 breast cancer (4 subjects), there was no fiveyear survival rate. All deaths were due to metastasis to the liver, lungs, brain, or bones. No deaths were due to local recurrence. This group of subjects did not develop any significant signs of toxicity as side effects of therapy. Other studies Back to the Table of Contents Several other studies that looked at the combination of TCM and western therapies in early stage breast cancer show that the five-year survival is greater in the combined approach. One study64 showed that in 134 women with stage II-III breast cancer, receiving surgery, chemotherapy and herbs, the five-year survival was 88.8%. In another study 62 patients with stage II-III breast cancer were divided into equal groups receiving standard surgery, radiation and chemotherapy with or without herbs. The herbs were taken for the whole duration of the observation. The five year survival was 93.5% (29/31) in the herb group compared to 32% (10/31) in the control group65. In our prior review66 we reported the studies that detail the effect of Chinese herbal medicine and acupuncture for the amelioration of side effects encountered during breast cancer treatment, modulation of immune functions, augmentation of bone marrow suppression and the treatment of pain. Fu Zheng Sheng Xue Tiao Yuan Tang (Boost the Upright, Raise Blood, and Regulate the Origin Decoction) Dang Shen (Radix Codonopsis Pilosulae) 15g, He Shou Wu (Radix Polygoni Multiflori) 10g, Nu Zhen Zi (Fructus Ligustri Lucidi) 20g, Gu Sui Bu (Rhizoma Gusuibu) 10g, Ji Xue Teng (Radix et Caulis Jixueteng) 15g, Mai Ya (Fructus Hordei Vulgaris Germinantus) 10g, Bai Zhu (Rhizoma Atractylodis Macrocephalae) 15g, Huang Jing (Rhizoma Polygonati) 15g. (Part 1) References Back to the Table of Contents 1 Eisenberg DM, Davis RB, Ettner SL et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. 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Cancer Treatment with Fu Zheng Pei Ben Principle. Fujian Science and Technology Publishing House, Fujian, 1992, p. 225-38. 53 Yu G, Liang F, Zhang D. The Combined TCM-WM prevention and treatment of malignant tumour marching towards 21st century.International Conference on Prevention and Treatment of Cancer with TCM-WM 1998, p.171. 54. Zhang D. Preventing and treating side-effects by chemo-and/ or radiotherapy over the past 40 years. International Conference on Prevention and Treatment of Cancer with TCM-WM 1998,p.174. 55 Liu M, Yao M, Shen P. Personal experience in herbal treatment of post-operative breast cancer. Affiliated Longhua Hospital, Shanghai College of TCM, 1991. 56 Wang G, Zhao L, Xu G. Observation on the Results of 216 Cases of Breast Cancer Treated with Integrated Chinese- Western Medicine China Chinese Medicine Research Institute, Guang An Men Hospital. Intermediate Medical Periodical [Zhong Ji Yi Kan] 1988, 23(8). 57 Yin X, Liu S, Tong J, et al An Analysis of 32 Cases of Breast Cancer Treated with a Combination of FACT and Kang Lai Te Injection. Qilu Journal of Oncology [Qi Lu Zhong Liu Za Zhi] 1999, Vol.6, No.2 58 Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Application. Harwood Academic Publishers, 1998, p. 319-20. 59 Yang H, Wang X, Yu L et al. Effects of Kang Lai Te (KLT) injection on cell proliferation kinetics and modulation of doxorubicin resistance. Kang Lai Te Injection: Pharmacology and Clinical Application, Cancer Institute, Zhejiang Medical University, 1999, p. 363-6 60 Han R. Developments in research on anti-cancer Chinese herbs. China New Herbs Journal (zhong guo xin yao za zhi), 1993, 2 (5): 1-7. 61 MJ Campbell, I Cohen, Hamilton B, Tagliaferri M, Shumaker M, Tripathy D. Antiproliferative Effects of Chinese Medicinal Herbs on Breast Cancer Cells, Proceedings of the American Association of Cancer Research (AACR) 62 Lei Q, Song Q, Fa D, et al. Observations on 77 cases of Breast Cancer Treated with the Chinese Herb Teng Huang. Jiang Xi Province Committee on Teng Hunag Anti-cancer Research. Cancer Prevention and Treatment Research: 1986, 13(2) 63 Zhou M, Wu Y, Liu Y. Integrated Chinese-Western Medicine Treatment for Late-Stage Breast Cancer: An Analysis of 14 Cases. Zhong Guo Zhong Xi Yi Jie He Za Zhi [China Integrated Medicine Journal] 1995, 15(4) 64 Chinese Medicine Research Institute, Guang An Men Hospital Oncology Department. An Analysis of 134 Cases of Breast Cancer Treated with Chinese-Western Integrated Medicine. Zhong Yi Zha Zhi [Chinese Medicine Journal] 1985, 26 (3) 65 Wang Q, He S. 31 cases of breast cancer treated with integrated Western-Chinese medicine. Ai Zheng [Cancer], 1990, 9(3): 238. 66 Tagliaferri M, Cohen I, Tripathy D. Complimentary and alternative medicine in early stage breast cancer. Seminars in Oncology 2001, 28(1): 121-134. 67 Vickers A, Goyal N, Harland R, et al. Do certain countries produce only positive results? A systematic review of controlled trials. Controlled Clinical Trials 1998, 19:159-166. 68 Tang J, Zhan S, Ernst E. Review of randomized controlled trials of traditional Chinese medicine. BMJ, 1999, 17 July, 319: 160-1. 69 Adler S. Complimentary and Alternative Medicine Use Among Women with Breast Cancer. Medical Anthropology Quarterly, 1999, 13 (2): 214-222. 70 Powell CB, Cohen I, DalEra J, et al: Use of Herbs in Women Diagnosed with Ovarian Cancer (pre-published data from survey) at UCSF-Mt. Zion Gynecological Cancer Center, 1999. (Part 2) References Back to the Table of Contents 1 Cohen I,Tagliaferri M,Tripathy D:Traditional Chinese Medicine in the treatment of breast cancer.The Journal of Chinese Medicine 68,Feb 2002,40-49. Traditional Chinese Medicine in the Treatment of Breast Cancer 2 Ernst E,Cassileth BR:The prevalence of complementary/ alternative medicine in cancer.Cancer 83:777-782,1998 3 Adler S:Complementary and alternative medicine use among women with breast cancer. 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American J Chin Med 1995,23(1):71-80. 31 Zhu YP.Chinese Materia Medica:Chemistry,Pharmacology and Applications. Harwood Academic Publishers,Australia, 1998.p.473,558,641,437,70,263,174,129. 32 Zhu YP.Chinese Materia Medica:Chemistry,Pharmacology and Applications . Harwood Academic Publishers, Australia, 1998.p.354,159. 33 Zhang D,Zheng X and Wang Q:Clinical study on climacteric syndrome treated by acupuncture and moxibustion.Shanghai Journal of Acupuncture and Moxibustion 1999,3:29-32. 34 Hsu H.Hau D.Lin C. Effect of kuei pi tang on cellular immunocompetence of irradiated mice.American J Chin Med 1993 ,21(2):151-8. (Part 3) References Back to the Table of Contents 1 Cohen I,Tagliaferri M,Tripathy D:Traditional Chinese Medicine in the treatment of breast cancer.The Journal of Chinese Medicine 68,Feb 2002,40-49. Traditional Chinese Medicine in the Treatment of Breast Cancer 2 Tagliaferri M. Cohen I. Tripathy D. Complementary and alternative medicine in early-stage breast cancer. 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Intnl J of Orient Med 1999, March 24(1): 21- 23. 10 Yata N. Tanaka O. The effects of saponins in promoting the solubility and absorption of drugs. Oriental Healing Arts International Bulletin, 1988 Feb. 13(1):13- 22. 11 Shen J, Wenger N, Glaspy J. et al. Electroacupuncture for control of myeloablative chemotherapy-induced emesis: A randomized controlled trial JAMA. 2000 Dec 6;284(21):275561. 12 Cohen I. The Treatment of Women With Breast Cancer Undergoing Chemotherapy with Fu Zheng Principles- Analysis and Description, California Journal of Oriental Medicine (CJOM), June 1998: 19-21 13 Zhu YP. Chinese Materia Medica: Chemistry, Pharmacology and Applications. Harwood Academic Publishers, Australia, 1998, p. 48, 550- 1, 174, 513, 655, 516. 14 Chang HM, But PPH. Pharmacology and Applications of Chinese Materia Medica, Vol. I, II. World Scientific, Singapore, 1988. p. 1119 15 Pan M. Cancer Treatment with Fu Zheng Pei Ben Principle. 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J Neurol. 2002 Jan;249(1):9-17. 43 Zhang J, Zhang P: Treatment of 56 cases of shingles by point injection therapy. Shanghai J Acu Mox. 1: 23- 24, 1999 44 Shan B and Shao S: The clinical observation on treating peripheral nerve injury by electroacupuncture. Shanghai J Acu Mox. 1(5): 24- 26, 1999 45 Galantino ML, Eke-Okoro ST, Findley TW et al. Use of noninvasive electroacupuncture for the treatment of HIVrelated peripheral neuropathy: a pilot study. J Altern Complement Med. 1999 Apr;5(2):135-42. 46 Abuaisha BB, Costanzi JB, Boulton AJ. Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin Pract. 1998 Feb;39(2):11521. 47 Shan B and Shao S: The clinical observation on treating peripheral nerve injury by electroacupuncture. Shanghai J Acu Mox. 1(5): 24- 26, 1999 48 Zhen H. Li Y. Yuan S. Clinical observation on diabetic peripheral neuropathy treated by needling combined with drug. Shanghai J Acu Mox. 2000, 3(1): 13-6. 49 Li M. Wang X. Clinical observation on treatment of diabetic peripheral neuropathy with refined tianma duzhong capsule. J TCM 1999, 19(3): 182-4. 50 Valero V. Primary chemotherapy with docetaxel for the management of breast cancer. Oncology (Huntingt). 2002 Jun;16(6 Suppl 6):35-43. 51 Mamounas EP. NSABP Protocol B-27. Preoperative doxorubicin plus cyclophosphamide followed by preoperative or postoperative docetaxel. Oncology (Huntingt). 1997 Jun;11(6 Suppl 6):37-40. 52 Nbholtz JM, Pienkowski T, Mackey J et al. Phase III trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC 5- fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients: interim analysis of the BCIRG 001 study. Program/ Proceedings of the American Society of Clinical Oncology Volume 21, May 2002 abs. 141, p.36a). 53 Physician Desk Reference, Nov. 2001). 54 Li Z, Ibrahim N. K. Wang M et al. Colitis in breast cancer patients treated with taxane based chemotherapy (TBC): M.D. Anderson Cancer Center experience. Program/ Proceedings of the American Society of Clinical Oncology Volume 21, May 2002 abs. 226 p.57a). Supported in part by NIH/NCI P50CA 58207 About the Authors Back to the Table of Contents Isaac Cohen, L.Ac.,O.M.D.(American Acupuncture Center, Berkeley, CA) is one of the founders of the Complimentary and Alternative Medicine Program at the University of California at San Francisco ’s (UCSF) Carol Frank Buck Breast are Center. His private practice specialises in the treatment of breast cancer with the integration of Western and Chinese medicine. Isaac has spearheaded many clinical and laboratory studies to assess the biological activity and efficacy of Chinese herbs in the treatment of cancer. Mary Tagliaferri , M.D.,L.Ac., (University of California at San Francisco)is one of the founders of the Complimentary and Alternative Medicine Program at the University of California at San Francisco ’s (UCSF) Carol Frank Buck Breast are Center. She opened the first traditional Chinese medicine clinic at UCSF. She is a co-Investigator on numerous clinical trials and laboratory studies to assess the effect of Chinese medicine in breast cancer. Mary is a breast cancer survivor. Debu Tripathy , M.D. Professor of Medicine and Director, Breast Cancer Research Program University of Texas Southwestern Medical Center at Dallas He has been a principal investigator on numerous clinical trials assessing chemotherapeutic agents and biological oncogene-targeting treatments. Debu is one of the founders of the CAM research program at UCSF and is the principal investigator on number of trials to assess the effects of herbs for breast cancer.