Arsenicum album Induces Cell Cycle Arrest and Apoptosis, and Inhibits Epithelial-Mesenchymal Transition in Hormone-Dependent MCF7 Breast Cancer Cells.

BACKGROUND: Arsenic trioxide (As2O3) has been in therapeutic use since the 18th century for various types of cancers including skin and breast; however, it gained popularity following FDA approval for its use against acute promyelocytic leukemia. This present work was designed to evaluate the anti-cancer potential of a homeopathic potency of arsenic trioxide (Arsenicum album 6C) in hormone-dependent breast cancer. METHODS: Breast cancer cells (MCF7) were treated with Arsenicum album (Ars 6C) to evaluate its anti-proliferative and apoptotic potential. We examined the effect of Ars 6C on the cell cycle, wound healing, reactive oxygen species (ROS) generation, and modulation of expression of key genes which are aberrant in cancer. RESULTS: Treating breast cancer cells with Ars 6C halted the cell cycle at the sub-G0 and G2/M phases, which could be attributed to DNA damage induced by the generation of ROS. Apoptotic induction was associated with upregulation of Bax expression, with concurrent downregulation of the Bcl-2 gene. Ars 6C was also seen to reverse epithelial to mesenchymal transition and reduce the migration of breast cancer cells. CONCLUSION: The findings suggest that Ars has significant anti-proliferative and apoptotic potential against breast cancer cells. Further studies are required to elucidate the mechanism by which Ars exerts its effect in the in vivo setting.

Uptake of Recommendations for Posttreatment Cancer-Related Fatigue Among Breast Cancer Survivors.

BACKGROUND: Physical activity (PA) and psychosocial interventions are recommended management strategies for cancer-related fatigue (CRF). Randomized trials support the use of mind-body techniques, whereas no data show benefit for homeopathy or naturopathy. METHODS: We used data from CANTO (ClinicalTrials.gov identifier: NCT01993498), a multicenter, prospective study of stage I-III breast cancer (BC). CRF, evaluated after primary treatment completion using the EORTC QLQ-C30 (global CRF) and QLQ-FA12 (physical, emotional, and cognitive dimensions), served as the independent variable (severe [score of ≥40/100] vs nonsevere). Outcomes of interest were adherence to PA recommendations (≥10 metabolic equivalent of task [MET] h/week [GPAQ-16]) and participation in consultations with a psychologist, psychiatrist, acupuncturist, or other complementary and alternative medicine (CAM) practitioner (homeopath and/or naturopath) after CRF assessment. Multivariable logistic regression examined associations between CRF and outcomes, adjusting for sociodemographic, psychologic, tumor, and treatment characteristics. RESULTS: Among 7,902 women diagnosed from 2012 through 2017, 36.4% reported severe global CRF, and 35.8%, 22.6%, and 14.1% reported severe physical, emotional, and cognitive CRF, respectively. Patients reporting severe global CRF were less likely to adhere to PA recommendations (60.4% vs 66.7%; adjusted odds ratio [aOR], 0.82; 95% CI, 0.71-0.94; P=.004), and slightly more likely to see a psychologist (13.8% vs 7.5%; aOR, 1.29; 95% CI, 1.05-1.58; P=.014), psychiatrist (10.4% vs 5.0%; aOR, 1.39; 95% CI, 1.10-1.76; P=.0064), acupuncturist (9.8% vs 6.5%; aOR, 1.46; 95% CI, 1.17-1.82; P=.0008), or CAM practitioner (12.5% vs 8.2%; aOR, 1.49; 95% CI, 1.23-1.82; P<.0001). There were differences in recommendation uptake by CRF dimension, including that severe physical CRF was associated with lower adherence to PA (aOR, 0.74; 95% CI, 0.63-0.86; P=.0001) and severe emotional CRF was associated with higher likelihood of psychologic consultations (aOR, 1.37; 95% CI, 1.06-1.79; P=.017). CONCLUSIONS: Uptake of recommendations to improve CRF, including adequate PA and use of psychosocial services, seemed suboptimal among patients with early-stage BC, whereas there was a nonnegligible interest in homeopathy and naturopathy. Findings of this large study indicate the need to implement recommendations for managing CRF in clinical practice.

Computational and In Vitro Approaches to Elucidate the Anti-cancer Effects of Arnica montana in Hormone-Dependent Breast Cancer.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Use of homeopathic medicines for the treatment of cancers has increased in the last several years. Arnica montana is an anti-inflammatory homeopathic medicine used in traumatic conditions and because of this property we performed investigations for its potential as a chemotherapeutic agent against breast cancer. METHODS: An ethanolic extract of Arnica montana (mother tincture, MT), prepared according to the Homoeopathic Pharmacopoeia of India, was characterized by gas chromatography-mass spectroscopy (GC-MS), followed by computational (in silico) analysis using molecular docking, to identify specific compounds that can bind and modulate the activity of key proteins involved in breast cancer survival and progression. To validate the in silico findings, in a controlled experiment breast cancer cells (MCF7) were treated in vitro with Arnica montana and the cytotoxic effects assessed by flowcytometry, fluorescence microscopy, scratch assay, clonogenic potential and gene expression analysis. RESULTS: Phytochemical characterization of ethanolic extract of Arn MT by GC-MS allowed identification of several compounds. Caryophyllene oxide and 7-hydroxycadalene were selected for molecular docking studies, based on their potential drug-like properties. These compounds displayed selective binding affinity to some of the recognized target proteins of breast cancer, which included estrogen receptor alpha (ERα), progesterone receptor (PR), epidermal growth factor receptor (EGFR), mTOR (mechanistic target of rapamycin) and E-cadherin. In vitro studies revealed induction of apoptosis in MCF7 cells following treatment with Arn MT. Furthermore, treatment with Arn MT revealed its ability to inhibit migration and colony forming abilities of the cancer cells. CONCLUSION: Considering the apoptotic and anti-migratory effects of Arnica montana in breast cancer cells in vitro, there is a need for this medicine to be further validated in an in vivo model.

In Vitro Assessment of Homeopathic Potencies of Hydrastis canadensis on Hormone-Dependent and Independent Breast Cancer.

BACKGROUND: Breast cancer is the second leading cause of cancer-related deaths in women. Conventional treatment such as chemotherapy, hormonal therapy and radiotherapy has decreased the mortality rate among cancer patients but has also revealed long-term side effects. Drug resistance and toxicity to normal cells compound the problems associated with the use of modern medicines. Hence, complementary or alternative treatment options are being explored. The current study, using different homeopathic potencies of Hydrastis canadensis, was conducted to distinguish between any effects they might have on hormone-dependent and independent breast cancer. MATERIALS AND METHODS: The cytotoxic effect of homeopathic medicine Hydrastis on hormone-dependent (MCF 7) and hormone-independent (MDA-MB-468) breast cancer cells was assessed using viability and colony-forming assays after 48 or 72 hours of treatment. Flow cytometry-based Annexin V-PI (propidium iodide), caspase 3 and cell cycle analysis was performed following treatment of cells with mother tincture or various potencies of Hydrastis (1C, 2C, 30C, 200C). RESULTS: Different potencies of Hydrastis displayed selective cytotoxic effects against MCF 7 cells, but only marginal effects against MDA-MB-468. The maximum cytotoxicity was established in the case of 1C following 72 hours of treatment. Treatment of breast cancer cells revealed an increase in the G0/G1 cell population, along with an increase in the caspase 3 levels and induction of apoptosis. CONCLUSION: Hydrastis may have a selective cytotoxic effect against hormone-dependent breast cancer MCF 7 cells, leading to cell cycle arrest in the G0/G1 phase, which could be the plausible reason for the induction of apoptosis. The results need to be validated in vivo.

My best case: homeopathic management of adverse effects of tamoxifen.

BACKGROUND: Nearly half of patients discontinue tamoxifen hormone therapy early because of side effects, thus increasing the risk of breast cancer recurrence. Could a homeopathic treatment improve compliance? METHODS: A patient suffering from side effects of tamoxifen was seen in consultation every 2 months for 10 months by a senior homeopathic doctor and a registrar. RESULTS: Case analysis and repertorisation led to the identification of Pulsatilla as the simillimum drug and tamoxifen 7c as the etiological treatment. This treatment resulted in a rapid and lasting improvement of all the symptoms. CONCLUSIONS: The combination of a homeopathic medicine and a hetero-isotherapic illustrates both the principles of "similarity" and "the identical". It has proved to be an excellent response to the side effects of tamoxifen. By enhancing the patient's quality of life, this combined approach also improved adherence to treatment.

Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial.

PURPOSE: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF). METHODS: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization. RESULTS: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470). CONCLUSIONS: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.

Evidence that Extreme Dilutions of Paclitaxel and Docetaxel Alter Gene Expression of In Vitro Breast Cancer Cells.

BACKGROUND: Gene expression analysis of cells treated with extreme dilutions or micro amounts of drugs has been used to provide useful suggestions about biological responses. However, most of the previous studies were performed on medicines being prepared from a variety of herbal and metal sources. This study investigated the effects of ultramolecular dilution of the taxane anti-cancer drugs, which are not commonly used in homeopathic medicines, on mRNA expression profiles of five key genes (p53, p21, COX-2, TUBB2A and TUBB3) in the breast cancer cell line MCF-7. METHOD: MCF-7 cells were exposed to paclitaxel (Taxol) or docetaxel (Taxotere) preparations (6X, 5C and 15C dilutions prepared from pharmacological concentration of 25 nmol/L) for 72 hours. The cell culture groups were evaluated with the trypan blue dye exclusion method for the proliferation/cytotoxicity rates, immuno-staining ß-tubulin for microtubule organization, and reverse transcription polymerase chain reaction for gene expression levels.Fold-change in gene expression was determined by the ΔΔCt method. RESULTS: The administration of diluted preparations had little or no cytotoxic effect on MCF-7 cells, but altered the expression of genes analyzed with a complex effect. According to the ΔΔCt method with a five-fold expression difference (p < 0.05) as a cut-off level, ultra-high dilutions of paclitaxel and docetaxel showed differential effects on the studied genes with a concentration-independent activity. Furthermore, the dilutions disrupted the microtubule structure of MCF-7 cells, suggesting that they retain their biological activity. CONCLUSION: Despite some limitations, our findings demonstrate that gene expression alterations also occur with ultra-high dilutions of taxane drugs.

Treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may reduce joint pain and stiffness linked to aromatase inhibitors in women with early breast cancer: results of a pilot observational study.

OBJECTIVE: To determine the possible effect of two homeopathic medicines, Ruta graveolens 5CH and Rhus toxicodendron 9CH, in the prevention of aromatase inhibitor (AI) associated joint pain and/or stiffness in women with early, hormone-receptor positive, breast cancer. METHODS: This prospective, unrandomized observational study was carried out between April and October 2014. Women were recruited in two groups, according to which of the two study centres they attended: one receiving homeopathy in addition to standard treatment (group H) and a control group, receiving standard treatment (group C). All women were treated with an AI. In addition, women in group H also took Ruta graveolens 5CH and Rhus toxicodendron 9CH (5 granules, twice a day) up to 7 days before starting AI treatment. The homeopathic medicines were continued for 3 months. Demographic and clinical data were recorded using a self-assessment questionnaire at inclusion (T0) and 3 months (T3). Primary evaluation criteria were the evolution of scores for joint pain and stiffness, the impact of pain on sleep and analgesic consumption in the two groups after 3 months of treatment. RESULTS: Forty patients (mean age 64.9±8.1 years) were recruited, 20 in each group. Two-thirds of the patients had joint pain before starting AI treatment. There was a significant difference in the evolution of mean composite pain score between T0 and T3 in the two groups (-1.3 in group H vs. +3.4 in group C; p=0.0001). The individual components of the pain score (frequency, intensity and number of sites of pain) also decreased significantly in group H. Nine patients in group C (45%) vs. 1 (5%) in group H increased their analgesic consumption between T0 and T3 (p=0.0076). After 3 months of treatment, joint pain had a worse impact on sleep in patients in group C (35% vs. 0% of patients; p=0.0083). The differences observed in the evolution of morning and daytime stiffness between the two groups were smaller (p=0.053 and p=0.33, respectively), with the exception of time necessary for the disappearance of morning stiffness which was greater in group C (37.7±23.0 vs. 17.9±20.1 min; p=0.0173). CONCLUSION: These preliminary results suggest that treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may decrease joint pain/stiffness in breast cancer patients treated with AIs. A larger-scale randomized study is required to confirm these results.

Evaluating the anticancer activity and nanoparticulate nature of homeopathic preparations of Terminalia chebula.

BACKGROUND: Breast cancer is the most common cancer diagnosed among women and is the second leading cause of cancer death. Homeopathic medicines are part of the alternative medicines that are given as a supportive therapy in breast cancer. The objective of this study was to investigate the anticancer activity of commercially available homeopathic preparations of Terminalia chebula (TC) and evaluate their nanoparticulate nature. METHODS: Mother tincture (MT) and other homeopathic preparations (3X, 6C and 30C) of TC were tested for their effect on the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell growth assay was performed to analyze the effect of the different potencies on the growth kinetics of breast cancer cells. MT and 6C were evaluated for the presence of nanoparticles by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: MT decreased the viability of breast cancer (MDAMB231 and MCF7) and non-cancerous (HEK 293) cells. However, the other potencies (3X, 6C and 30C) decreased the viability of only breast cancer cells without affecting the viability of the non-cancerous cells. All the potencies, MT, 3X, 6C and 30C, reduced growth kinetics of breast cancer cells, more specifically at 1:10 dilution at 24, 48 and 72 h. Under SEM, MT appeared as a mesh-like structure whereas under TEM, it showed presence of nanoclusters. On the other hand, 6C potency contained 20 nm sized nanoparticles. CONCLUSION: The current study reports the anticancer activity of homeopathic preparations of TC against breast cancer and reveals their nanoparticulate nature. These preliminary results warrant further mechanistic studies at both in vitro and in vivo levels to evaluate the potential of TC as nanomedicine in breast cancer.

Anti-proliferative effects of homeopathic medicines on human kidney, colon and breast cancer cells.

OBJECTIVE: Homeopathy is controversial, due to the claims made for very high dilutions. Although several theories are proposed to understand the mechanisms of action, none are scientifically verified. This study aimed to investigate the efficacy of the selected homeopathic medicines in specific in vitro cancer models. METHODS: We assessed the cytotoxic activity of selected homeopathic medicines in mother tincture (MT), and ultramolecular dilution (30C, 200C, 1M and 10M) against cell lines deriving from tumors of particular organs, Sarsaparilla (Sars) on ACHN cells (human renal adenocarcinoma), Ruta graveolens (Ruta) on COLO-205 (human colorectal carcinoma), and Phytolacca decandra (Phyto) on MCF-7 (human breast carcinoma). Sars was also tested against Madin-Darby canine kidney (MDCK) cells (a non-malignant cell line). Cytotoxicity was measured using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) method, anti-proliferative activity by trypan blue exclusion assay, apoptosis determined by dual staining the cells with ethidium bromide (EB) and acridine orange (AO) dyes. RESULTS: MTs and ultra-diluted preparations of the three homeopathic medicines had highly significant effects in the respective cancer cell lines, producing cytotoxicity and a decrease in cell proliferation. The effects were greatest with the MTs, but in all cases and persisted, although to a lesser degree in the ultra-diluted molecular preparations. Sars showed no effect on MDCK cells. In the homeopathic medicine treated cultures, hallmarks of apoptosis were evident including, cell shrinkage, chromatin condensation and DNA fragmentation. CONCLUSION: This study provides preliminary laboratory evidence indicating the ability of homeopathic medicines as anticancer agents. Further studies of the action of these homeopathic remedies are warranted.

Complementary and alternative medicine in cancer patients: characteristics of use and interactions with antineoplastic agents.

PURPOSE: Our objectives were to analyze the use of complementary and alternative medicine (CAM) in cancer patients and to describe the incidence and characteristics of interactions between CAM and antineoplastic agents. METHODS: We performed an observational study in cancer outpatients at a university hospital. Variables were collected through a 22-item questionnaire. Potential interactions between CAM and antineoplastic agents were analyzed using the Lexicomp®, the About Herbs®, and the summary of product characteristics. Mechanism of action, reliability, and the potential clinical effect of interactions were analyzed. RESULTS: The study population comprised 937 patients, of whom 65% used CAM (70.6% herbal products, 25.8% dietary supplements, and 3.6% homeopathy). Female sex, younger age, and breast cancer were associated with more frequent use of CAM. The primary source of information about CAM was friends and family (43.5%). A total of 335 (57.1%) patients did not tell their doctor that they took CAM. The five most common CAM were chamomile, green tea, pennyroyal mint, linden, and rooibos. At least one interaction between CAM and antineoplastic agents was reported by 65.0% of CAM users (33.9% of all patients). Depending on the mechanism of action, 80% of CAM diminished the metabolism of the antineoplastic agents. CONCLUSION: Our results reveal a high incidence of interactions between CAM and antineoplastic agents. The most frequent CAM were herbal products. Family and friends were the primary sources of information that led patients to start taking CAM, and more than half of the patients did not tell their doctor that they were taking CAM.

Utilization of complementary and alternative medicine (CAM) by women with breast cancer or gynecological cancer.

BACKGROUND: Complementary and Alternative Medicine (CAM) has become increasingly popular among cancer patients. The prevalence of CAM use differs worldwide and depends on different sociodemographic and medical characteristics. Findings on predictors for CAM use and its benefits for quality of Life (QoL) have been inconclusive in recent studies. OBJECTIVE: The aim of the study was to determine the prevalence and methods of CAM use in breast cancer (BC) and gynecological cancer (GC) patients, to compare CAM users vs. non-CAM users regarding their sociodemographic and medical characteristics, and to investigate the relationship between CAM use and QoL. METHODS: In a sub-analysis from a multicenter, cross-sectional study in Germany, we examined 1,214 female cancer patients (897 with BC and 317 with GC). We obtained data from self-reports via standardized questionnaires and measured QoL with the EORTC QLQ-C30. RESULTS: In total, 565 of the 1,214 patients (46.5%) used some form of CAM. Its use was higher in BC than in GC patients (48.6% vs. 40.7%). In both cancer groups, the users evaluated CAM as being helpful (BC: 60.8%, GC: 59.6%) The most frequently used CAM methods were vitamins/minerals/micronutrients, homeopathy, and mistletoe therapy. CAM users are younger, more highly educated, and financially better off than non-CAM users. They are also characterized by having been diagnosed with cancer a longer time ago, being at more advanced stages of the disease, and experiencing higher distress levels. CAM use is significantly associated with a lower global health status/ QoL in GC patients. Predictors for CAM use are: high level of vocational education, middle or high monthly income, time span since diagnosis of more than 12 months, the status of currently ongoing chemotherapy or hormone therapy treatment, and distress. CONCLUSION: Our data support the findings of previous studies and highlight the need to develop a consistent CAM definition with respect to comparability and evaluation of CAM services. More longitudinal studies are desirable to establish viable associations between CAM use and relevant outcomes such as QoL or disease management.

Can treatment with Cocculine improve the control of chemotherapy-induced emesis in early breast cancer patients? A randomized, multi-centered, double-blind, placebo-controlled Phase III trial.

BACKGROUND: Chemotherapy induced nausea and vomiting (CINV) remains a major problem that seriously impairs the quality of life (QoL) in cancer patients receiving chemotherapy regimens. Complementary medicines, including homeopathy, are used by many patients with cancer, usually alongside with conventional treatment. A randomized, placebo-controlled Phase III study was conducted to evaluate the efficacy of a complex homeopathic medicine, Cocculine, in the control of CINV in non-metastatic breast cancer patients treated by standard chemotherapy regimens. METHODS: Chemotherapy-naïve patients with non-metastatic breast cancer scheduled to receive 6 cycles of chemotherapy including at least three initial cycles of FAC 50, FEC 100 or TAC were randomized to receive standard anti-emetic treatment plus either a complex homeopathic remedy (Cocculine, registered in France for treatment of nausea and travel sickness) or the matching placebo (NCT00409071 clinicaltrials.gov). The primary endpoint was nausea score measured after the 1st chemotherapy course using the FLIE questionnaire (Functional Living Index for Emesis) with 5-day recall. Secondary endpoints were: vomiting measured by the FLIE score, nausea and vomiting measured by patient self-evaluation (EVA) and investigator recording (NCI-CTC AE V3.0) and treatment compliance. RESULTS: From September 2005 to January 2008, 431 patients were randomized: 214 to Cocculine (C) and 217 to placebo (P). Patient characteristics were well-balanced between the 2 arms. Overall, compliance to study treatments was excellent and similar between the 2 arms. A total of 205 patients (50.9%; 103 patients in the placebo and 102 in the homeopathy arms) had nausea FLIE scores > 6 indicative of no impact of nausea on quality of life during the 1st chemotherapy course. There was no difference between the 2 arms when primary endpoint analysis was performed by chemotherapy stratum; or in the subgroup of patients with susceptibility to nausea and vomiting before inclusion. In addition, nausea, vomiting and global emesis FLIE scores were not statistically different at any time between the two study arms. The frequencies of severe (Grade ≥ 2) nausea and vomiting were low in our study (nausea: P: 17.6% vs C: 15.7%, p=0.62; vomiting: P: 10.8% vs C: 12.0%, p=0.72 during the first course). CONCLUSION: This double-blinded, placebo-controlled, randomised Phase III study showed that adding a complex homeopathic medicine (Cocculine) to standard anti-emetic prophylaxis does not improve the control of CINV in early breast cancer patients.

Complementary and alternative medicines use by Scottish women with breast cancer. What, why and the potential for drug interactions?

BACKGROUND: Despite the increased use of complementary and alternative medicine (CAM) by breast cancer patients, there is little published information regarding CAM use in the Scottish breast cancer population. METHODS: A questionnaire comprising five sections--demographics; perceived health status, prescribed medicines; use, indications, satisfaction and expenditure on CAMs; attitudes towards and factors associated with CAM use; and attitudinal statements--was issued to patients attending the Aberdeen Breast Clinic. RESULTS: A total of 453 questionnaires were distributed and 360 (79.5%) returned. Respondents were prescribed a mean of 3.2 medicines (95% CI 2.83-3.47). With regard to CAM use, 33.1% of respondents reported current use, 36.4% prior use, and 30.6% reported never having used CAMs. The key indications for use were general well being, boosting immune system and cancer prophylaxis, with high levels of satisfaction reported. The strongest association for CAM use was use by friends and family and higher educational attainment (p < 0.001). Supplements with estrogenic activity, such as soya or red clover, were taken by 29% of respondents. Herbs (echinacea, pomegranate, peppermint, chamomile, grapefruit, garlic, ginseng) that have the potential to interact with adjuvant endocrine therapies (tamoxifen, anastrazole, letrozole, exemestane) were being taken by 38% of treated patients. CONCLUSION: The level of CAM use by Scottish breast cancer patients is similar to that reported from other countries, although there are marked differences in the type, nature and frequency of specific CAM therapies. Higher patient education level and use by family and friends were significantly associated with CAM use. The high level of use of potentially disease modifying or interacting herb supplements may be of concern.

Attention Dysregulation in Breast Cancer Patients Following a Complementary Alternative Treatment Routine: A Double-Blind Randomized Trial.

INTRODUCTION: Breast cancer patients and survivors frequently report fatigue, emotional, and cognitive disturbances, which reduce performance at all levels of occupation and make life quality issues a considerable clinical concern. The aim of this study is to evaluate attention and emotion regulation across radiotherapy period and the possible effects of complementary alternative medicine (CAM). METHODS: Fifty-seven patients with unilateral breast cancer underwent surgery and systemic chemotherapy before participating in this double-blind randomized study. Two thirds were given CAM (n = 38) while the rest received placebo (carrier only, n = 19). Patients' attention and anxiety were physiologically tested at baseline, 2 and 4 weeks during the radiation period as well as 1-month after the end of radiation session. RESULTS: Both groups showed similar levels of anxiety with no significant differences at baseline nor post-radiotherapy. Long-term significant recovery of attention performance was observed in the CAM patients, accompanied by a similar tendency in anxiety level, measured by the eye-blink probability. CONCLUSIONS: This study physiologically validates the attention impairment reported among breast cancer survivors; also, it depicted a beneficial late-effect of a routine CAM on attention dysregulation. The suggested non-invasive physiological measures can physiologically monitor patients' psychological and cognitive well-being as well as evaluate the beneficial effect of CAM in breast cancer patients by assessing their coping ability to support the treatment plan. Thus, the results have potential clinical implications on patients' and survivors' quality of life. TRIAL REGISTRATION: NIH, NCT02890316. Registered July 2016, http://www.ClinicalTrials.gov.

[Scientific medicine and care relationship: From the therapeutic alliance to the therapeutic effect of the alliance]. / Médecine scientifique et relation de soin : de l'alliance thérapeutique à l'effet thérapeutique de l'alliance.

The new paradigm of precision medicine in oncology questions today the respective place of evidence-based medicine and doctor-patient relationship. Based on the results of a randomized study comparing the efficacy of a homeopathic molecule in the prevention of nausea and vomiting induced by chemotherapy in non-metastatic breast cancer, this article extends and develops the discussion of maintaining an unresolved tension between medical art and medical science, between care and cure. This tension sets a base for the authors of the therapeutic alliance in medicine, defined as a dialectic constantly adjourned between the alliance of the doctor with the patient and his therapy, and the therapeutic effect of this alliance. Because if a policy or a public opinion were to promote an exclusively rational medicine deprived of the field of relation to care, or on the contrary a medicine based only on clinical sense and intuition, then respectively the ethics of care and the progress of therapy would be threatened. It is advisable to be aware of erring from the truth, amplified today by social networks, as much due to a tide of scientific positivism, as an excess of the "good caring soul". Taking into account the therapeutic alliance makes it possible to no longer oppose scientific medicine and care relationship.

Non-hormonal interventions for hot flushes in women with a history of breast cancer.

BACKGROUND: Hot flushes are common in women with a history of breast cancer. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects. The efficacy of non-hormonal therapies is still uncertain. OBJECTIVES: To assess the efficacy of non-hormonal therapies in reducing hot flushes in women with a history of breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, CINAHL, PsycINFO (August 2008) and WHO ICTRP Search Portal. We handsearched reference lists of reviews and included articles, reviewed conference proceedings and contacted experts. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing non-hormonal therapies with placebo or no therapy for reducing hot flushes in women with a history of breast cancer. DATA COLLECTION AND ANALYSIS: Two authors independently selected potentially relevant studies, decided upon their inclusion and extracted data on participant characteristics, interventions, outcomes and the risk of bias of included studies. MAIN RESULTS: Sixteen RCTs met our inclusion criteria. We included six studies on selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors, two on clonidine, one on gabapentin, two each on relaxation therapy and homeopathy, and one each on vitamin E, magnetic devices and acupuncture. The risk of bias of most studies was rated as low or moderate. Data on continuous outcomes were presented inconsistently among studies, which precluded the possibility of pooling the results. Three pharmacological treatments (SSRIs and SNRIs, clonidine and gabapentin) reduced the number and severity of hot flushes. One study assessing vitamin E did not show any beneficial effect. One of two studies on relaxation therapy showed a significant benefit. None of the other non-pharmacological therapies had a significant benefit. Side-effects were inconsistently reported. AUTHORS' CONCLUSIONS: Clonidine, SSRIs and SNRIs, gabapentin and relaxation therapy showed a mild to moderate effect on reducing hot flushes in women with a history of breast cancer.

Effects of homeopathic preparations on human prostate cancer growth in cellular and animal models.

The use of dietary supplements for various ailments enjoys unprecedented popularity. As part of this trend, Sabal serrulata (saw palmetto) constitutes the complementary treatment of choice with regard to prostate health. In homeopathy, Sabal serrulata is commonly prescribed for prostate problems ranging from benign prostatic hyperplasia to prostate cancer. The authors' work assessed the antiproliferative effects of homeopathic preparations of Sabal serrulata, Thuja occidentalis, and Conium maculatum, in vivo, on nude mouse xenografts, and in vitro, on PC-3 and DU-145 human prostate cancer as well as MDA-MB-231 human breast cancer cell lines. Treatment with Sabal serrulata in vitro resulted in a 33% decrease of PC-3 cell proliferation at 72 hours and a 23% reduction of DU-145 cell proliferation at 24 hours (P<.01). The difference in reduction is likely due to the specific doubling time of each cell line. No effect was observed on MDA-MB-231 human breast cancer cells. Thuja occidentalis and Conium maculatum did not have any effect on human prostate cancer cell proliferation. In vivo, prostate tumor xenograft size was significantly reduced in Sabal serrulata-treated mice compared to untreated controls (P=.012). No effect was observed on breast tumor growth. Our study clearly demonstrates a biologic response to homeopathic treatment as manifested by cell proliferation and tumor growth. This biologic effect was (i)significantly stronger to Sabal serrulata than to controls and (ii)specific to human prostate cancer. Sabal serrulata should thus be further investigated as a specific homeopathic remedy for prostate pathology.

Homeopathic medicines do not alter growth and gene expression in prostate and breast cancer cells in vitro.

BACKGROUND: Homeopathy is an alternative medical system practiced in all parts of the world. Although several theories are proposed to explain the mechanisms of action, none are scientifically verified. In this study, the authors investigate the effect of selected homeopathic remedies often used to treat prostate and breast cancer. MATERIALS AND METHODS: The authors investigated the effect of the homeopathic medicines Conium maculatum, Sabal serrulata, Thuja occidentalis, Asterias, Phytolacca, and Carcinosin on prostate and breast cancer cell (DU-145, LNCaP, MAT-LyLu, MDA-MB-231) growth and on gene expression that regulates apoptosis, using MTT and multiprobe ribonuclease protection assay. RESULTS: None of the homeopathic remedies tested in different potencies produced significant inhibitory or growth-promoting activity in either prostate or breast cancer cells. Also, gene expression studies by ribonuclease protection assay produced no significant changes in mRNA levels of bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, or FasL after treatment with homeopathic medicines. CONCLUSIONS: The results demonstrate that the highly diluted homeopathic remedies used by homeopathic practitioners for cancer show no measurable effects on cell growth or gene expression in vitro using currently available methodologies.