Erin Sweet

Breast cancer and the immune system

This article reviews the evidence that the functioning of both the innate and the adaptive immune system plays a role in preventing relapse in women with breast cancer. Lymphocytes, including T cells, T regulatory cells, and natural killer cells, and their cytokine release patterns are implicated in both primary prevention and recurrence of breast cancer. Cancer prognosis may be related to immune system functional status. The hypothesis that the immune system has a causal role in breast cancer etiology is supported by epidemiologic, preclinical, and clinical research. Empirical support for the concept that immune status and immunomodulatory therapy have important roles in comprehensive breast cancer treatment is provided.

Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer

Introduction. Orally administered preparations from the Trametes versicolor (Tv) mushroom have been hypothesized to improve immune response in women with breast cancer after standard chemotherapy and radiotherapy. Methods. A phase I, two-center, dose escalation study was done to determine the maximum tolerated dose of a Tv preparation when taken daily in divided doses for 6 weeks after recent completion of radiotherapy. Eleven participants were recruited and nine women completed the study. Each cohort was comprised of three participants given one of three doses of Tv (3, 6, or 9 grams). Immune data was collected pre- and postradiation, at 3 on-treatment time points and after a 3-week washout. Results. Nine adverse events were reported (7 mild, 1 moderate, and 1 severe), suggesting that Tv was well tolerated. Immunological results indicated trends in (1) increased lymphocyte counts at 6 and 9 grams/day; (2) increased natural killer cell functional activity at 6 grams/day; (3) dose-related increases in CD8+ T cells and CD19+ B cells , but not CD4+ T cells or CD16+56+ NK cells. Conclusion. These findings show that up to 9 grams/day of a Tv preparation is safe and tolerable in women with breast cancer in the postprimary treatment setting. This Tv preparation may improve immune status in immunocompromised breast cancer patients following standard primary oncologic treatment.

Involvement in decision-making about treatment and ovarian cancer survivor quality of life

PURPOSE This study sought to better understand the long-term effects on womens health related quality of life (HRQOL) of involvement in decision-making about their surgical and chemotherapeutic treatments for ovarian cancer treatment and about follow-up care after treatment. METHODS Using a cross-sectional survey design, a sample of 219 ovarian cancer patient/survivors from Western Washington who were between 3 months and ten years post-diagnosis were recruited via a mailed survey sent by their gynecological oncologist and interviewed about their ovarian cancer treatment, use of Complementary and Alternative Medicine (CAM), Health related quality of life, and their involvement in decision-making about their cancer treatment and follow-up care. RESULTS Multivariate regression analyses revealed age, but not stage of cancer to be a significant predictor of perceived involvement in decision-making about ovarian cancer treatment and follow-up. Age also predicted CAM use with older patients using herbal CAM, and younger patients using CAM activities and CAM providers (p<0.5). Controlling for demographic, disease, and treatment characteristics involvement in decision-making about surgery and follow-up care were associated with better mental health in survivorship (p<0.05). Involvement in decision-making about use of CAM and about lifestyle health changes was associated with greater vitality and better role-emotional health in survivorship (respectively; both; p<0.05). CONCLUSIONS As has been found in studies of breast cancer survivors, perceived involvement in decision-making about ovarian cancer treatment including surgery and follow-up care after treatment is associated with better quality of life for cancer survivors. Involvement in decision-making about the use of CAM and about changes in lifestyle health practices also appear to help survivors emotional health related quality of life. Prospective studies are needed to determine the mechanisms by which perceived involvement in decision-making about treatment might influence survivor quality of life.

Dangerous Combinations: Ingestible CAM Supplement Use During Chemotherapy in Patients with Ovarian Cancer

OBJECTIVE Some ingestible complementary and alternative medicine (CAM) supplements, including herbal remedies, teas, and vitamins, have biological activities that make them likely to interact poorly with conventional chemotherapeutic treatments. This study surveyed women with ovarian cancer to document the extent to which women use ingestible CAM supplements and conventional chemotherapeutic treatments that are believed to be of potential concern when used together. METHODS A total of 219 patients with ovarian cancer who received care from 1 of 2 participating conventional oncology practices were surveyed about CAM use during and after ovarian cancer treatment. RESULTS A total of 200 women reported having chemotherapy to treat their ovarian cancer. Of those, 79 (40%) reported using 1 or more CAM supplements that could be cause for concern when taken with 1 or more of the chemotherapy medications they were receiving. Many patients took multiple supplements of potential concern. Of these women, 42% (n=33) consulted with a conventional provider and 24% (n=19) consulted with a CAM provider about the contraindicated supplements they used. CONCLUSION Although it is not clear that any of these contraindicated combinations of CAM and conventional therapy actually caused adverse outcomes, increased toxicities, or reduced the effectiveness of primary therapies, all these effects are possible given the substances being used in combination. Research is needed to understand the real risk associated with CAM and conventional polypharmacy. If risks associated with CAM use prove substantial, then improved systems to assure that all women get advice regarding supplement use during ovarian cancer treatment will be needed.

Immune Defects in Breast Cancer Patients after Radiotherapy

The purpose of this study was to evaluate the immune status of women with stage I-III breast cancer after receiving external beam radiotherapy (RT). Fourteen stage I-III, estrogen or progesterone receptor-positive or-negative (FER/PR +\-), postsurgical breast cancer patients undergoing a standard course of chemotherapy and radiation were studied. Complete blood counts (CBC) with differential, phagocytic activity, natural killer (NK) cell functional activity, and tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma cytokine activity were measured immediately before and for the six weeks following the completion of radiation therapy. Fatigue levels after completion of RT were measured using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale. Nonparametric statistical methods (Wilcoxon rank and Spearman correlations) were used to analyze the data. Compared with postchemotherapy, following the completion of RT, these breast cancer patients showed lymphopenia, low functional activity of natural killer lymphocytes, decreased monocyte phagocytic activity, and decreased TNF-alpha production but no neutropenia, no anemia, and no change in interferon-gamma production. Lymphocyte count did not return to normal by the end of the 6-week post-RT observation period. The severity of lymphopenia and low natural killer cell activity was related to RT area but not radiation dose. Patients did not report significant fatigue levels for the 6 weeks after completing RT. Significant decreases in the numbers and functions of cells from both the innate and adaptive immune system were detected following a standard course of radiation therapy for the treatment of breast cancer. Immune deficits in lymphocyte populations and TNF-alpha production, should they persist, may have consequences for immune response to residual or recurrent malignancy following completion of conventional treatment. The use of adjunctive immune therapies which target these specific defects may be warranted in the post-treatment period.

Adverse events associated with complementary and alternative medicine use in ovarian cancer patients.

Introduction. Many women with ovarian cancer are choosing to include complementary and alternative medicine (CAM) substances in conjunction with their conventional treatment for ovarian cancer. Many oncologists express concern that the adjunct use of CAM substances may be detrimental to the achievement of therapeutic levels of chemotherapy leading to increases in drug toxicity, under-treatment of disease or other adverse events. In an effort to ascertain the extent of the potential problem with simultaneous use of CAM with conventional treatment we undertook comprehensive systematic review of published case reports describing CAM-related adverse events among ovarian cancer patients. Study design. This article describes a systematic literature review. Methods. The Natural Medicines Comprehensive Database (NMCD). PubMed, EMBASE® and the Cochrane Central Register of Controlled Trials (CCTR) were systematically reviewed for research articles pertaining to case reports describing adverse events in patients, and clinical trials which examined the effects of herbs and supplements used during cancer treatment. Results. Only one case report and one clinical trial were identified which met our inclusion criteria and were relevant to the current investigation. Conclusion. Although there are concerns about the potential for adverse events related to concurrent use of CAM substances during conventional treatment we found few case reports and clinical trials in the literature which support this.

Complementary and alternative medicine use by breast cancer patients at time of surgery which increases the potential for excessive bleeding.

Objective. The use of complementary or alternative medicine has increased greatly over the last decade. This study describes a cross-sectional survey of women with breast cancer to describe their use of herbs and supplements that might have placed them at elevated risk for bleeding at the time of their primary treatment surgery for breast cancer. Methods. We present cross-sectional survey results from a cohort of 316 women with breast cancer. The participants included a convenience sample of 98 women who received integrative oncology treatment from local providers and a larger group of women recruited from the local cancer registry who were matched on their similarity to the integrative oncology patients’ demographic characteristics and stage of cancer at time of diagnosis. Results. Almost 16% of women with breast cancer report using one or more herbs or supplements thought to potentially increase their risk for adverse bleeding-related outcomes at the time of their primary surgical treatment. This does not include the 22% who used fish and flaxseed oils, which were at one time thought to increase risk for bleeding but for which there is now evidence to suggest that they are safe. Conclusion. Further research is needed to better understand the risks associated with use of a variety of herbs and supplements among women approaching surgery.

Can We Demonstrate That Breast Cancer “Integrative Oncology” Is Effective? A Methodology to Evaluate the Effectiveness of Integrative Oncology Offered in Community Clinics

Background. Many women diagnosed with breast cancer receive both standard cancer treatment and care from providers trained in the emerging field of medicine called integrative oncology (IO) in which science-based complementary and alternative medical therapies are prescribed by physicians. The effectiveness of IO services has not been fully studied, so is yet unknown. Purpose. Determine if a matched, case-controlled prospective outcomes study evaluating the efficacy and safety of breast cancer IO care is feasible. Methods. Methodological proof of principle requires demonstration that (1) it is possible to find matched control breast cancer patients using the Surveillance, Epidemiology and End Results (SEER) Program’s western Washington Cancer Surveillance System (CSS) and (2) an IO clinic can recruit breast cancer patients into a matched controlled study. Results. A pilot study was conducted in 2008 (n = 14) to determine if matched controlled women could be identified in the western Washington SEER database. All 14 women who were approached agreed to participate. The cases were matched to the CSS along 5 variables: age and stage at diagnosis, race, and marital and Estrogen Receptors/Progesterone Receptors (ER/PR) status. Multiple matches were found for 12 of the 14 participants. Conclusion: A prospective cohort study with a matched comparison group is a feasible and potentially rigorous study design with high patient acceptability. It may provide valuable data for the evaluation of the effectiveness of IO care on patient health, relapse rate, and health-related quality of life (HRQOL). A federally funded matched case controlled outcomes study is currently under way at Bastyr University and the Fred Hutchinson Cancer Research Center.

Breast Cancer Integrative Oncology Care and Its Costs

Background. Naturopathic oncology in conjunction with conventional treatment is commonly referred to as integrative oncology (IO). Clinics directed by oncology board certified NDs (Fellows of the American Board of Naturopathic Oncology or FABNOs) provide high-quality data for describing IO therapies, their costs and measuring clinical outcomes. Purpose. To describe the types of IO therapies prescribed to breast cancer patients by ND FABNO physicians. Study participants (n = 324). Women who sought care at 1 of 6 naturopathic oncology clinics in Washington State were asked to enroll in a prospective 5 year observational outcomes study. Methods. Medical records were abstracted to collect treatment recommendations and cost data. Results. More than 72 oral or topical, nutritional, botanical, fungal and bacterial-based medicines were prescribed to the cohort during their first year of IO care. Trametes versicolor was prescribed to 63% of the women. Mind-body therapy was recommended to 45% of patients, and 49% received acupuncture. Also, 26% were prescribed injectable therapy, including mistletoe, vitamin B complex (12%), IV ascorbate (12%), IV artesunate (7%), and IV nutrition and hydration (4%). Costs ranged from

The Use of Complementary and Alternative Medicine Supplements of Potential Concern during Breast Cancer Chemotherapy.

1594/year for early-stage breast cancer to