Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Menopause

Women in the waiting list control group will receive usual care. They will complete questionnaires during a period of 6 months. After completion of the last questionnaire they will be offered the opportunity to follow the EVA-Online program.

The CBT/Relaxation program (EVA-Online) consists of 6 online sessions intended to be completed weekly over a 6 week period. The program comprises the following elements: (1) information and advice about symptoms (e.g., hot flushes, night sweats and sexual functioning); (2) monitoring and modifying precipitants; (3) relaxation and stress reduction; (4) cognitive restructuring of unhelpful thoughts and (5) encouraging helpful behavioral strategies (e.g., pacing activities). Throughout the program women will be asked to spend an hour a week to read the session and fill in the assignments and to spend 30 minutes per day on homework exercises (eg, filling in a hot flush/night sweats diary, practicing relaxation techniques).

Participating women will first undergo a 30 minute phone interview with a trained therapist before they start the online program. The same therapist will provide weekly feedback and support.

The content of the self-management CBT/Relaxation program is the same as the guided version of the program as described above, but without weekly guidance by a trained therapist. The women allocated to the self-management intervention will work through the program independently.

Internet-based cognitive behavioral therapy

EVA-Online

Neil K. Aaronson, PhD

Hester S.A. Oldenburg, PhD

Marc Van Beurden, PhD

The current study will evaluate systematically the efficacy and cost-effectiveness of two internet-based CBT/relaxation programs (one guided, the other self-managed) in reducing the severity of menopausal symptoms and improving copings skills with regard to hot flushes and night sweats as well as improving sexual functioning, improving quality of sleep, reducing emotional distress and improving quality of life in younger breast cancer patients who experience treatment-induced menopause.

Background: Breast cancer is the most common cancer among women in the Netherlands, with approximately 14.000 new cases reported in 2011 (1). Nearly 30% of all women with breast cancer are premenopausal at the time of diagnosis (2). Ovarian damage is a major long-term sequela of chemotherapy in premenopausal women (3,4). Ovarian failure induced by chemotherapy and/or endocrine treatment leads to an earlier onset of menopause, with age and duration of treatment being its strongest predictors (5).

Premature menopause is a major concern of younger women undergoing (adjuvant/preventive) therapy for cancer (6). Primary menopausal symptoms include hot flushes, night sweats, vaginal dryness, decreased libido, dysuria and urinary incontinence. Secondary symptoms include insomnia due to night sweats, dyspareunia because of vaginal dryness, weight gain, and psychological distress (3,7,8). Previous studies have indicated that the severity of hot flushes is increased in women who experience transition into menopause during cancer treatment or after PBSO, compared to women going through natural menopause (9,10,11).

Among menopausal symptoms, hot flushes are considered to be the most disruptive, with prevalence rates between 63% and 80% in breast cancer patients (7,12-15). Moreover, vasomotor symptoms are an important reason why some women discontinue tamoxifen treatment (16,17). Hormonal replacement therapy (HRT) is highly effective in alleviating vasomotor symptoms associated with menopause (18). However, HRT is contraindicated in women with a history of breast cancer (19), even after prophylactic bilateral salpingo oophorectomy (PBSO) (20).

There is increasing evidence that behavioral interventions have a positive impact on symptoms in women with naturally occurring and treatment-induced menopause (21-27). A cognitive behavioral therapy (CBT) intervention including information about symptoms, monitoring and modifying precipitants, relaxation and stress management, cognitive restructuring of unhelpful assumptions and automatic thoughts, and encouraging helpful behavioral strategies has been found to be beneficial in the alleviation of menopausal symptoms in women with breast cancer (25,26), but compliance with face-to-face CBT programs can be problematic (26). A promising approach is to make this form of CBT more accessible and feasible for participants by having it available via the internet. Although the efficacy of CBT for this patient population has been demonstrated in the form of face-to-face group therapy, its efficacy has not been investigated when delivered via an internet platform in an individual setting.

Design. For this trial patients will be recruited from several hospitals in the Netherlands (predominantly Amsterdam region). Participants will be randomly allocated to either the guided intervention group, the self-management group or the control group (N = 83 per group). Upon completion of the study, the patients assigned to the control group will be given the opportunity to undergo the internet-based cognitive behavioral therapy program.

Women in the two intervention and control group will be asked to complete a battery of questionnaires prior to randomization (TO), at 10 weeks (T1) and at 6 months (T2).

Study measures. The primary outcomes are menopausal complaints, as assessed with a menopausal complaints questionnaire, the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES), and hot flushes and night sweats as assessed by the Hot Flushes Rating Scale (HFRS). The secondary study outcomes are sexuality problems (the Sexual Activity Questionnaire (SAQ)); sleep quality (The Groningen Sleep Quality Score (GSQS)); psychological distress (The Hospital Anxiety and Depression Scale (HADS)) and health related quality of life (The Medical Outcome Study 36-Item Short Form-36 Health Survey (SF-36)).

Patients' evaluation of the intervention program. The women in both intervention groups will be asked to provide their opinion of the internet-based CBT program at the 10 week evaluation point. All these women will be asked to complete a short questionnaire about the perceived efficacy of and satisfaction with the intervention program, whether they would suggest any changes to the program, and if they would recommend it to other women experiencing symptoms of premature menopause. In addition, telephone interviews (30 minutes) will be held with women who: (1) stated in the questionnaire that the intervention did not have the desired effect; and/or (2) gave the intervention a low rating (\<6) and/or (3) would not recommend the program to others.

Cost effectiveness. The cost-effectiveness of the internet-based guided CBT versus the internet-based self-management CBT versus usual care will be expressed as: (1) cost per patient with a clinically relevant significant reduction on the HFRS and (2) cost per quality adjusted life year (QALY) gained.

Sample size and statistical power calculations: In total, 248 women will be recruited into the study, to allow for an attrition rate of approximately 20% (i.e., women who discontinue participation in the study entirely, including failure to complete all follow-up questionnaires; those women who discontinue participation in one of the groups but complete the follow-up assessments will be included in the analysis). Thus, a minimum of 130 women will be available for the primary intention-to-treat analysis. With a total sample of 130 women (65 per group), the study will have 80% power to detect an effect size of 0.5 with a p value of 0.05 (28).

Statistical analyses: Analyses will first be performed to evaluate the comparability of the intervention groups (guided versus self-management) and control group at baseline in terms of sociodemographic and clinical characteristics. ANOVA tests or appropriate non-parametric statistics will be used, depending on the level of measurement. If, despite the stratified randomization procedures, the groups are found not to be comparable on one more background variables, those variables will be employed routinely as covariates in subsequent analyses.

We will evaluate between-group differences over time in self-reported endocrine symptoms, sexual functioning, psychological distress, sleep quality and HRQOL. Scores for the FACT-ES, the HFRS, the SAQ, the HADS, the GSQS, and the SF-36 and the utility version of the SF-36, the SF-6D will be calculated according to published scoring algorithms.We will compare both intervention groups with the control group over time using multilevel procedures with repeated measures, using a restricted maximum likelihood (REML) solution to model specific contrasts between groups and follow-up assessment (29). Within each multilevel model the control group will be the reference category. Differences in mean change scores over time between the intervention groups and the control group will be accompanied by effect sizes (ES). As indicated previously, the FACT-ES and the HFRS will be used as the primary study endpoints, and the remaining measures will be considered as secondary endpoints. The p-value for overall model effects will be set at 0.05, and for specific contrasts at 0.01, lowering the risk of Type errors due to multiple testing.

All analyses will be conducted on an intention-to-treat (ITT) basis. In addition, per-protocol (PP) analyses will be performed on patients who met criteria for minimal compliance with the intervention(s). Supplementary analyses will be carried out in which data relating to compliance with the program elements is taken into account. Specifically, we will determine whether the level of compliance (based on completed homework assignments and self-report data) is associated significantly with the changes over time in symptom relief, sexuality, psychological distress, sleep quality, and cost-effectiveness. In addition the potential mediating effect of hot flush beliefs and behaviors will be examined through mediator analysis.

A cost-effectiveness analysis (CEA) will be performed using a validated health economic model as developed for use in the EVA-Trial (30). The analysis will consider the societal perspectives, the third-party payer perspective and the healthcare system perspective in comparing the effectiveness and costs of web-based CBT for alleviating treatment-induced menopausal symptoms versus waiting list control. Effectiveness data as gathered from the trial will be combined with the cost data from the cost-diary and hospital administration data.

Internet-based Cognitive Behavioral Therapy for Breast Cancer Patients With Climacteric Symptoms

A Randomized Controlled Trial of Internet-based Cognitive Behavioral Therapy for Breast Cancer Patients With Climacteric Symptoms

Overall levels of menopausal symptoms are assessed by using the FACT-ES

Vasomotor symptoms are assessed with the Hot Flush Rating Scale (HFRS)

The overall levels of sexual functioning are assessed with the Sexual Activity Questionnaire (SAQ)

Psychological distress is assessed with the Hospital Anxiety and Depression Scale (HADS)

Sleep quality is assessed with the Groningen Sleep Quality Scale (GSQS)

Hot flush frequency is assessed with the frequency subscale of the Hot Flush Rating Scale (HFRS)

Health related quality of life is assessed with the SF-36 questionnaire

Dutch Cancer Society

The Netherlands Cancer Institute

Symptoms and General Pathology

Hot Flashes

Amenorrhea

Menstruation Disturbances

immediate start of hydrotherapy (self treatment) in immediate treatment group (SBG)

start of hydrotherapy (self treatment) after waiting period of 12 weeks

2-5 applications of hydrotherapy according to Kneipp rules (self application) per day

hydrotherapy according to Kneipp rules

Bernhard Uehleke, Dr.med. Dr.rer.nat. (PhD)

Breast cancer survivors often suffer from climacteric symptoms caused by treatment or diagnosis of their disease.

Hormone replacement therapy is contraindicated and other pharmacological options may also include the risk of stimulating hormone receptors. Hydrotherapy following the guidelines of naturopathy by S. Kneipp is a non-pharmacological treatment option which may influence climacteric symptoms by affecting the regulation of body temperature. In this study, the regular self application of hydrotherapy after initial training by a professional will be evaluated for its efficacy, practicability, and compatibility.

Patients should use 2-5 different treatment options per day and fulfill a diary for symptoms and adherence to self-treatment for 12 weeks.

Hydrotherapy Against Menopausal Symptoms in Breast Cancer Survivors

Prospective Randomized Feasibility Study on the Self Application of Hydrotherapy to Treat Menopausal Symptoms Caused by Breast Cancer Therapy

Charite University, Berlin, Germany

Heidelberg University

Head Complementary & Integrative Medicine, Dep. 4.2

Recurrence

Antineoplastic Agents

Antihypertensive Agents

All Drugs and Chemicals

Tibolone

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Anabolic Androgenic Steroids

Anabolic Agents

tibolone

placebo

Postmenopausal women with a history of breast cancer often suffer from climacteric symptoms such as hot flushes and sweating episodes. Conventional hormone therapy is not allowed in such patients because there are indications that hormones may cause breast cancer to recur.

Tibolone is a steroid with estrogenic, progestogenic and androgenic activity and is registered for treatment of climacteric complaints. Tibolone has a pharmacologic and clinical profile that is different from conventional hormones. In contrast to conventional hormones, tibolone does not increase breast density and causes less breast pain.

The LIBERATE study is a study in which the safety and efficacy of tibolone has been investigated in postmenopausal women that have been treated for breast cancer.

A growing proportion of women diagnosed with early stage breast cancer seek help with vasomotor and sexual complaints. Frequently, these symptoms result from adjuvant cancer treatment, irrespectively whether this is hormonal (e.g. tamoxifen, aromatase inhibitors), cytotoxic, or surgical (oophorectomy) in nature. Estrogen-containing hormone therapy is effective, but considered unsafe. Non-hormonal therapy is less effective. Tibolone, which does not increase mammographic breast density, has proven to be effective and thus could be an important treatment option for women persistently seeking help.

The objective of this trial is to demonstrate safety, efficacy and tolerability of oral 2.5 mg tibolone daily in breast cancer patients, who, after surgery, have no evidence of disease and who suffer from climacteric complaints. Primary study endpoint is breast cancer recurrence, including primary contralateral breast cancer. Secondary outcome variables include menopausal symptoms, bone mineral density and health-related quality of life.

Patients were eligible for this study when they had been surgically treated within the previous 5 years for histologically confirmed T1-3, N0-2, M0 breast cancer and had to have vasomotor symptoms, with a last menstruation at least 12 months before (or bilateral oophorectomy).

The LIBERATE Trial has been designed to show non-inferiority of tibolone compared to placebo. Adequate sample size was estimated to be at least 1500 subjects in each arm, assuming a breast cancer recurrence rate of 5% per year in the first 3 years and an dropout rate of 5% per year.

The LIBERATE Study has successfully included the appropriate number of women with the proper risk profile so that significant results can be obtained in relation to safety and efficacy of tibolone in breast cancer patients with menopausal complaints.

Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)

A Multinational, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Trial to Investigate Safety and Efficacy of Tibolone (Org OD14) in Women With Climacteric Symptoms and a History of Breast Cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Internet-based Cognitive Behavioral Therapy for Breast Cancer Patients With Climacteric Symptoms	NCT02672189	Climacteric Sym... Breast Cancer S...	EVA-Online	18 Years - 55 Years	The Netherlands Cancer Institute
Internet-based Cognitive Behavioral Therapy for Breast Cancer Patients With Climacteric Symptoms	NCT02672189	Climacteric Sym... Breast Cancer S...	EVA-Online	18 Years - 55 Years	The Netherlands Cancer Institute
Hydrotherapy Against Menopausal Symptoms in Breast Cancer Survivors	NCT00243607	Amenorrhea Hot Flashes	hydrotherapy ac...	18 Years -	Heidelberg University
Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)	NCT00408863	Breast Cancer Climacteric Sym...	tibolone placebo	- 75 Years	Organon and Co
Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)	NCT00408863	Breast Cancer Climacteric Sym...	tibolone placebo	- 75 Years	Organon and Co

Spots Global Cancer Trial Database for climacteric symptoms