Weaning Dexmedetomidine in Non-ICU Areas: An Implementation Effort.

OBJECTIVES: To develop and implement clinical practice guidelines for safely weaning dexmedetomidine infusions in non-ICU areas. DESIGN: Development, implementation, and analysis of effectiveness of clinical practice guidelines. SETTING: Quaternary care academic free-standing pediatric hospital. PATIENTS: Children, otherwise medically ready for transfer to non-ICU areas, who were undergoing a planned wean of a dexmedetomidine infusion. INTERVENTIONS: Subject matter experts developed evidence-based guidelines for weaning dexmedetomidine in patients whose critical phase of illness had resolved. MEASUREMENTS AND MAIN RESULTS: Searches identified no prospective studies of dexmedetomidine weaning. We identified two retrospective reviews of withdrawal symptoms and one on the use of clonidine. There were case studies on withdrawal symptoms. Guidelines were piloted on a cohort of 24 patients while in the ICU. The guidelines were then implemented in non-ICU areas for patients undergoing dexmedetomidine weaning after ICU transfer. Over a 2-year period (October 1, 2018, to September 30, 2020), 63 patients (1 mo to 18 yr old) successfully weaned dexmedetomidine in non-ICU areas. The median time to discontinuation of dexmedetomidine after transfer to non-ICU areas was 5.8 days (interquartile range, 4.75-15 d). Fifty-eight percent (n = 41) of all patients were considered high risk for dexmedetomidine withdrawal based on the dose, duration of exposure, and the risk of experiencing physiologic detriment with more than mild withdrawal. Twenty-nine patients (46%) exhibited no signs or symptoms of withdrawal while weaning per guidelines. For those with signs and symptoms of withdrawal, the most common were tachycardia (n = 26, 40%), agitation (n = 9, 14%), and hypertension (n = 9, 11%). CONCLUSIONS: Weaning dexmedetomidine in non-ICU areas is feasible and can be accomplished safely even among pediatric patients at high risk for withdrawal using standardized weaning guidelines. At our institution, implementation was associated with reduced ICU length of stay for patients recovering from critical illness.

Effects of Vitamin D Use on Health-Related Quality of Life of Breast Cancer Patients in Early Survivorship.

BACKGROUND: Vitamin D supplements may prevent recurrence, prolong survival, and improve mood for women with breast cancer, although evidence for these effects is preliminary. METHODS: This report describes vitamin D supplement use by 553 breast cancer patient/survivors (193 who used a naturopathic oncology [NO] provider and 360 who did not) participating in a matched cohort study of breast cancer outcomes. RESULTS: We found that more than half of breast cancer patients reported using vitamin D supplements. Women who received care from NO providers in early survivorship may be more likely to use vitamin D supplements ( P < .05). Approximately 30% of breast cancer patients with blood levels recorded in their medical chart were potentially vitamin D deficient (<30 ng/mL). Vitamin D supplement use at study enrollment was associated with higher levels of self-reported health-related quality of life (HRQOL) at enrollment ( P < .05) and predicted better HRQOL at 6-month follow-up ( P < .05). Sufficient blood levels of vitamin D recorded between enrollment and follow-up were also associated with better HRQOL at follow-up ( P < .05). CONCLUSIONS: Vitamin D supplementation by breast cancer patients is common both during and after treatment for breast cancer, but deficiency may also be common. NO and conventional providers may be able to promote vitamin D sufficiency through vitamin D supplementation and by encouraging healthy solar exposure. Further studies should be undertaken examining whether vitamin D supplementation and higher blood levels might improve HRQOL among women with breast cancer in early survivorship.

Use of Integrative Oncology, Involvement in Decision-Making, and Breast Cancer Survivor Health-Related Quality of Life in the First 5 Years Postdiagnosis.

OBJECTIVE: This study sought to describe changes in the health-related quality of life (HRQOL) of women who do and do not seek naturopathic oncology (NO) complementary and alternative medicine (CAM) care during and immediately after breast cancer treatment, and to explore the predictive role of NO CAM care, demographic characteristics, and involvement in decision-making on HRQOL in breast cancer survivors. METHODS: Matched cohorts of breast cancer survivors who did and did not choose to supplement their breast cancer treatment with NO care within 2 years of diagnosis participated. NO users were identified through naturopathic doctors' clinics and usual care (UC) controls with similar prognosis were identified through a cancer registry. The registry provided information about all participants' age, race, ethnicity, marital status, stage of cancer at time of diagnosis, date of diagnosis, and use of conventional medical treatments (surgery, chemotherapy, radiation, and endocrine therapy). Data of participants' self-reported involvement in decision-making and HRQOL were collected at study enrollment and at 6-month follow-up. RESULTS: At 6-month follow-up, the NO patients reported significantly more involvement in decision-making about care and better general health than did UC patients ( P < .05). Self-reported involvement in decision-making about cancer treatment was associated with better role-physical, role-emotional, and social-functional well-being ( P < .05). Race, age, marital status, and congruence of preferred and achieved levels of involvement also predicted aspects of HRQOL in breast cancer survivors ( P < .05). CONCLUSIONS: Both NO CAM care and involvement in decision-making about cancer treatment may be associated with better HRQOL in breast cancer survivors.

Do Women With Breast Cancer Who Choose Adjunctive Integrative Oncology Care Receive Different Standard Oncologic Treatment?

PURPOSE: To determine if women with breast cancer who choose adjunctive naturopathic oncology (NO) specialty care receive different standard oncologic treatment when compared with breast cancer patients who receive only standard care. PARTICIPANTS: Women with breast cancer stages 0 to 4, aged 18+ who spoke English and sought care from outpatient naturopathic doctor clinics were enrolled in an observational study of clinical and quality of life outcomes. Women who sought NO care 2 or more times within the first 2 years postdiagnosis were identified as NO cases. A matched comparison group of breast cancer patients were identified using the Western Washington Cancer Surveillance System(CSS). METHODS: A longitudinal cohort design. In addition to self-report data, the CSS provided data on demographics, stage at the time of diagnosis, and initial treatment. Oncology medical records were abstracted in order to provide additional information on standard oncologic treatment for all participants. RESULTS: Cohorts were well matched with regard to demographic, histologic, and prognostic indicators at the time of diagnosis. Approximately 70% of women in both cohorts received standard oncologic care that met the National Comprehensive Cancer Network guidelines. There were no statistically significant differences between the cohorts in treatment received. Fewer women in the NO cohort with estrogen receptor-positive breast cancer appear to have received antiestrogen therapy. CONCLUSIONS: Women in both cohorts appear to receive guideline-concordant care. However, women who receive adjunctive NO care may be less likely to receive antiestrogen therapy.

Nurse Practitioner-Administered Chloroprocaine in Children with Postoperative Pain.

BACKGROUND: Pain is a complex physical and emotional experience. Therefore, assessment of acute pain requires self-report when possible, observations of emotional and behavioral responses and changes in vital signs. Peripheral nerve and epidural catheters often provide postoperative analgesia in children. Administration of chloroprocaine (a short acting local anesthetic) via a peripheral nerve or epidural catheter allows for a comparison of pain scores, observations of emotional and behavioral responses and changes in vital signs to determine catheter function. AIMS: The aims of this study are to describe the use chloroprocaine injections for testing catheters; patient response; and how changes to pain management are guided by the patient response. METHODS: This study describes the use of chloroprocaine injections to manage pain and assess the function of peripheral nerve or epidural catheters in a pediatric population. We examined 128 surgical patients, (0-25 years old), who received chloroprocaine injections for testing peripheral nerve or epidural catheters. Patient outcomes included: blood pressure, respiratory rate, heart rate and pain intensity scores. RESULTS: There were no significant adverse events. The injection guided intervention by determining the function of regional analgesia in the majority (98.5%) of patients. DISCUSSION: Chloroprocaine injections appear to be useful to evaluate functionality of peripheral nerve and epidural catheters after surgery in a pediatric population.

The 'cause' of my cancer, beliefs about cause among breast cancer patients and survivors who do and do not seek IO care.

OBJECTIVE: We sought to describe survivors' beliefs about the cause of their breast cancer and to test the hypothesis that beliefs about cancer's cause are associated with treatment preferences in accordance with the common sense model of self-regulation of health and illness. METHODS: Breast cancer survivors (n = 552) participating in an observational study of cancer outcomes responded to an open-ended question about the cause of their cancer. Of these, 245 women had sought treatment from complementary and alternative integrative oncology (IO) clinics, and 307 women did not. RESULTS: Women frequently described theories for their cancer's cause including genetics and family history (31%), stress and coping (31%), toxins and chemicals (27%), a variety of lifestyle and epidemiological risk factors, and randomness (17%). Self-reported beliefs about cancer's cause differed among women in association with their use of IO. IO users were somewhat more likely to describe stress and poor coping as causes of their cancer and less likely to describe random chance as a cause of cancer (p < 0.05). CONCLUSIONS: Beliefs about the cause of cancer change over time and may predict decisions to use specific treatment including complementary and alternative medicine and IO. Copyright © 2015 John Wiley & Sons, Ltd.

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 $1594/year for early-stage breast cancer to $6200/year for stage 4 breast cancer patients. Of the total amount billed for IO care for 1 year for breast cancer patients, 21% was out-of-pocket. CONCLUSIONS: IO care for women with breast cancer consists of botanical and mushroom oral therapies, parenteral botanical and nutrient therapy, mind-body medicine and acupuncture. IO clinic visits and acupuncture are partially paid for by medical insurance companies.

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

Objective. While many Complementary and Alternative Medicines (CAM) are unlikely to interact negatively with conventional oncology treatment, some ingestible CAM substances have biological activities that may reduce the effectiveness of chemotherapy or radiation. This study surveyed women with breast cancer in order to document the extent to which women with breast cancer use these CAM substances of concern concurrently with conventional treatments. Methods. A total of 398 women completed a survey describing their use of CAM at various time points in their cancer treatment. This report focuses on a subsample of 250 women receiving chemotherapy or radiation who reported using specific one or more of several chemotherapies. Results. Of those participating, 104 (43.7%) of those receiving chemotherapy (n = 238) and 45 (32.3%) of those receiving radiation (139; 58.4% of all patients) reported using one or more CAM substances that could be cause for concern when taken concurrently. Conclusion. Research is needed to understand the real risks associated with CAM and conventional polypharmacy. If risks associated with CAM conventional polypharmacy use prove to be substantial then improved systems to assure all women get advice regarding herb and supplement use during breast cancer treatment appear to be needed.

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.

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.

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.

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: 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: 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.

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 women's 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 survivor's 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.

A pilot study of website information regarding aromatase inhibitors: dietary supplement interactions.

OBJECTIVES: Patients who have hormone receptor-positive breast cancer and who are taking aromatase inhibitors (AIs) should understand the benefits and risks of concomitant dietary supplement (DS) use. The International Society for Integrative Oncology (SIO) encourages patients to discuss DS use with their health care practitioners. The objective was to conduct a pilot study rating Internet websites from the perspective of health care practitioners for information about AI-DS interactions. DESIGN: Five (5) Internet websites suggested by SIO were evaluated using the DISCERN instrument rating tool. The available AI-DS information on these websites was rated by 4 evaluators: 2 naturopathic doctors, 1 oncology pharmacy resident, and a pharmacy student. RESULTS: The overall rankings ranged from 1.6 to 3.9, with considerable variability in the type of information available from the websites. The interevaluator rankings of the websites ranged from 0.44 to 0.89. The evaluators consistently found the most reliable, unbiased, and comprehensive information on AI-DS interactions at the Natural Medicines Comprehensive Database and Memorial Sloan-Kettering Cancer Center websites. However, more than one database was needed for provision of optimal patient information on AI-DS interactions. CONCLUSIONS: In order to effectively advise patients regarding AI-DS interactions, more than one website should be evaluated to assess the potential efficacy and safety of DS in women whose breast cancer is being treated with an AI.

An analysis of toxicology and medical journal conflict-of-interest polices.

Basic science and medical journals are increasingly requiring authors to disclose financial interests they have in the subject matter of contributed articles and letters. A comparison of journal conflict-of-interest (COI) policies can provide insight into published reports of low compliance rates and inconsistencies in disclosures by the same author found in different journals. The objective of this article is to compare the criteria, specificity, and scope of COI polices in toxicology and medical journals. We studied the COI policies of 47 toxicology and 180 medical journals catalogued in Ulrich's International Periodicals Directory for criteria of competing interests, types of submissions covered, monetary or time thresholds for reporting, and penalties for violations. Indicators were constructed for rating policy specificity, author discretion, and policy scope. Written COI policies were found in 87% if the toxicology and 84% of the medical journals; 15% and 28% of the toxicology and medical journals, respectively, were explicit about the type of content covered by the policy; 20% and 29%, respectively, included a monetary threshold for reporting purposes; the level of author discretion for reporting COIs was found to be high in 46% of the toxicology and 41% of the medical journals respectively. The level of specificity for more than 75% of the written journal COI policies for both fields was minimal or practically nil, and the scope of more than 80% of the policies was minimal to narrow. Lack of specificity, high author discretion, and restricted scope were found to be prevalent among COI policies of toxicology and medical journals.

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.

Trametes versicolor mushroom immune therapy in breast cancer.

Data from multiple epidemiologic and clinical studies on immune effects of conventional cancer treatment and the clinical benefits of polysaccharide immune therapy suggest that immune function has a role in breast cancer prevention. Immune therapy utilizing the polysaccharide constituents of Trametes versicolor (Tv) as concurrent adjuvant cancer therapy may be warranted as part of a comprehensive cancer treatment and secondary prevention strategy.

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.