Integrative Traditional Chinese Medicine and Chemotherapy: Survival Data in Node-Positive and Metastatic Breast Cancer Michael Broffman, LAc and Michael McCulloch, MPH, LAc OUR DEFINITION OF INTEGRATION Medical practitioners, East and West, search for a "magic bullet"-a cure that will revolutionize the practice and therapeutic value of medicine. While there is, as yet, no such single cure for breast cancer, there is growing evidence that "magical combinations" offer the most promise. An early example of a therapy that brought together separately investigated agents into one treatment for breast cancer was the CMF protocol as pioneered by Bonnadonna.(1) Similarly, combination strategies have become the dominant practice in alternative medicine. The need for combination strategies has arisen out of clinical observations that single-agent alternative therapies for breast cancer are rarely successful. In our clinical practice at the Pine Street Chinese Benevolent Association, we provide multi-modality alternative protocols for patients with breast cancer being treated by nearby oncology specialists. We use Traditional Chinese Medicine (TCM) as the underlying organizing principle to design our protocols. In our experience, this integration can deliver more favorable results than either modality used alone. To illustrate these observations, we conducted a retrospective case review of 288 patients treated in our clinic between 1987 and 1991. We report here 5- and 10-year follow-up data on these patients with node-positive Stage II and III, and metastatic Stage IV breast cancer. PATIENTS AND METHODS Between 1987 and 1991, we treated 288 women with breast cancer (Stage II: 109, Stage III: 86, and Stage IV: 93 cases). All cases were infiltrating adenocarcinoma, both ductal and lobular subtypes. Diagnosis and pathology were determined by: * observation and palpation of the breast * mammography * fine needle aspiration * incisional or excisional biopsy * bone scan * estrogen receptor and progesterone receptor assay All women received: * radical or modified mastectomy with lymph node dissection * adjuvant chemotherapy protocol. (CMF: cyclophosphamide, methotrexate and 5-fluorouracil for 6 months, or CAF: cyclophosphamide, doxorubicin, and 5-fluorouracil for 4 to 6 months. In this retrospective review, our research goal was to examine whether a multi-modality protocol based on TCM integrated with CMF or CAF chemotherapy (vs. CMF/CAF alone) could increase 5-year and 10-year survival rates in women with stage II, III, and IV breast cancer. We selected as external controls patients treated with CMF or CAF alone, matched as closely as possible to our study cohort in age, estrogen receptor (ER) status, node status, use of Tamoxifen (TMX) treatment, and time the study was conducted. We provided the same multi-modality protocol in all 288 cases (see TABLE III). Close follow-up helped to achieve an estimated 95 percent patient compliance rate. Both the CMF and the CAF chemotherapy protocols were on a 21-day cycle. We also provided patients with the following description of our protocol design and rationale, based on TCM chronotherapy and clinically observed energetic patterns. Part I -Days one through three of 21-day chemotherapy cucle. The goal is enhancing circulation to facilitate tumor drug delivery. Suggestions: relaxation, stress reduction, Qi-Gong. Part II is days four through six. Chemotherapy has killed off numerous cells in the body, both cancer cells and normal cells. A salt and soda bath helps discharge toxins and drug metabolites through the skin: 1 cup of baking soda and 1 cup sea salt added to a warm bath. Soak for 20 to 30 minutes daily. Also helpful is dry skin brushing to stimulate and cleanse the lymphatic system. Use a long-handled natural vegetable bristle brush, passing over the skin in a clean sweeping motion (not back and forth) towards the heart. Avoid the face. This is done twice per day, before Qi-Gong practice. Part III-days seven through ten. Numerous dead cells are piling up in the body and need to be removed. The white blood cells hit their nadir (lowest point). The amount of dead cells accumulating often exceeds the body's natural ability to cleanse them out on its own. Therefore the main goal in this part is to assist the body in discharging and cleansing. In this way these dead cells will not be in the way of the next round of chemotherapy. Salt-and-soda baths and skin brushing continue, along with Qi-Gong. Part IV-days 11 to day 21. During this time the blood counts and much of the body's physiology will start to normalize. The goal at this time is to strengthen and enhance the immune system. RESULTS Comparisons In all disease stages, our multi-modality protocol appeared to compare favorably with other studies treating with either CMF or CAF alone. We believe that the use of multi-modality protocols that combine surgery and chemotherapy with integrative TCM has benefited our patients. DISCUSSION Limitations This case review is a retrospective study, limited by availability of medical record data. Additional data such as the number of positive nodes per patient would have allowed us to make more specific comparisons. Furthermore, our Stage IV data have the potential for significant bias due to our not having available either the time from breast cancer diagnosis to first recurrence, or elapsed time from first recurrence to entry in our study. By comparing our patients to those from other published studies using external controls treated with CMF or CAF alone, our study is subject to substantial limitations in matching study and control patients. Although CMF and CAF are similar in their efficacy, some studies show a slight survival and response trend in favor of CAF, (2,3) and others show a significant advantage. (4,5) Our findings may be more precisely rendered by comparing only those of our patients treated with CMF to the CMF external controls and similarly, for those patients treated with CAF. We had some missing data in the CMF dosages, which could introduce some bias in comparing our patients to those treated with chemotherapy alone. Even though Pine Street patients were temporally matched to external control cohorts, and thus likely to have received similarly dosed chemotherapy dosages, differences in dosages could have biased survival outcomes in one direction or the other. Matching patients was also made difficult by the varying percentages of patients in the control studies who had used Tamoxifen. Furthermore, a higher percentage of estrogen receptor positive patients were present in our Stage II (as compared to the Scottish study) and Stage IV study cohorts (as compared to the German study). This may have conferred a higher survival advantage to our patients. Note that when we aggregated our Stage II and Stage III patients in order to make a comparison with the Canadian study by Levine (in which more patients were ER-positive), there was a smaller survival advantage to our patients than in the previous comparisons. Additional bias could be present due to the higher percentage of post-menopausal women in our study cohorts. Our clinical practice focuses on the use of integrative protocols. With our own patients, we were not able to design a trial that would randomize patients to chemotherapy alone. A prospective study could help minimize the potential for bias through the randomization process. Background Discussion: Chrono-Therapeutics Every metabolic event undergoes rhythmic changes in time (thus, the term "chrono"). Drug bio-availability, host immunity and hormonal levels all demonstrate variability according to circadian rhythm. Early authors in the Chinese medical literature first described chrono-therapeutics as a treatment strategy in two Chinese medical classics: The Yellow Emperor's Classic of Internal Medicine (Huang Di Su Wen Nei Jing)" and the Classic On Difficult Issues (Nan Jing). In designing our protocols, we began with the original Chinese theories, adding where possible data on human physiological functions and drug pharmacokinetics from modern published sources.(6) These protocols are based on a combination of traditional Chinese medical literature, clinical studies from Chinese journals, (7) published in-vitro studies, in-vivo animal studies, and published human trials. However, some protocol elements are not directly linked in the published literature with their intended uses as we have applied them. Although science has made considerable progress in the treatment of cancer, more progress is still needed. We believe that "out-of-the-box" thinking in cancer care can combine published science, anecdotal observations and active patient and doctor collaboration to achieve better clinical outcomes. Our clinical experience suggests that treatments timed according to the circadian rhythm may offer a long-term survival advantage. Our treatment strategies are based on the three-pronged principle of (1) boosting host immunity, (2) decreasing the body burden of drug metabolite toxicity and (3) enhancing the cytotoxic effect of chemotherapeutic drugs. Improving cancer treatment remains an important challenge. In future, we hope to formally test multi-modality protocols in prospective trials. Pine Street Chinese Benevolent Association was established in San Anselmo, California in 1982. Pine Street houses a medical clinic, clinical research center, medical information library, and an Integrative Medical Tumor Board. Michael Broffman, LAc is clinical director, and Michael McCulloch, MPH, LAc research director. Other publications include a meta-analysis of TCM vs. alpha-interferon on the treatment of chronic hepatitis B (currently being reviewed by the British Medical Journal). Current research projects in progress at our nonprofit research office are formal survival analyses (breast, lung, colon, and stomach cancers), and the development of an early detection screening method for lung cancer using a professionally trained dog to detect exhaled volatile organic chemicals. For more information call 415/407-1357. Integrative Study Cochrane Review, 1/05 Remember we are NOT Doctors and have NO medical training. 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