Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cognitive Behavioral Therapy (CBT) and Physical Exercise for Climacteric Symptoms in Breast Cancer Patients Experiencing Treatment-Induced Menopause: a Multicenter Randomized Trial
Brief Summary: Background: Breast cancer is the most common form of cancer among women in the Netherlands. Approximately 11,000 women are diagnosed with breast cancer annually, of whom about 30% are below 50 years of age. Premenopausal women with breast cancer treated with chemotherapy or hormonal therapy may experience a premature onset of the menopause. Estrogen deficiency following adjuvant treatments leads to primary endocrine symptoms, including vasomotor and urogenital problems. Secondary symptoms include insomnia due to night sweats, dyspareunia due to vaginal dryness, weight gain, and psychological distress. The symptoms resulting from accelerated estrogen withdrawal can be pronounced and severe, and may adversely affect women's sexual functioning, body image, and overall HRQL. Healthy women who enter natural menopause are often prescribed hormone replacement therapy (HRT) to alleviate vasomotor and sexual symptoms. However, due to possible tumor-promoting effects, HRT is contraindicated for patients with a history of breast cancer. For these women, non-hormonal medications are frequently prescribed to treat vasomotor symptoms. Although these medications have been shown to yield moderate symptom relief, they also have a number of bothersome side effects. To alleviate urogenital symptoms, local vaginal moisturizing or estrogen cream is often prescribed. There is growing evidence that cognitive behavioral therapy (CBT) including relaxation techniques, and physical exercise may effectively reduce vasomotor symptoms in naturally occurring menopause. CBT and relaxation techniques are aimed primarily at the modification of precipitants of hot flushes and at stress management. Physical exercise on a regular basis affects neurotransmitters, which regulate central thermoregulation.

Purpose: The proposed study will evaluate the efficacy of a supportive intervention program in alleviating menopausal symptoms, improving sexual functioning and enhancing the quality of life of younger women (\< 50 years) with breast cancer who have become prematurely menopausal as a result of their treatment. Specifically, the study will evaluate CBT including relaxation (A), physical exercise (B), and a combination of A and B.

Plan of investigation: This multicenter study will employ a prospective, full-factorial design. In total, 325 consenting women will be randomized to group A, group B, group AB or a usual care, 'waiting list' control group (N = 81-81 per group). Upon completion of the study, the patients assigned to the control group will be given the opportunity to undergo either the A or B intervention program. The program will begin with a structured assessment of the target symptoms: hot flushes, night sweating and vaginal dryness. The overriding goal of the intervention is to provide symptomatic women with information skills and support to manage their symptoms more effectively. For group A, the intervention will consist of 6 weekly group CBT sessions of 1.5 hours, of 15 minutes of daily homework and a booster session at 3 months. The CBT will focus on understanding and self-control of menopausal symptoms. Relaxation techniques (paced respiration and muscle relaxation) will focus on the reduction of sympathetic nervous system activity, and are expected to have a positive impact on the frequency and intensity of hot flushes. For group B, the intervention will be an individually tailored, 12 week home-based physical exercise program of 2.5-3 hours per week, with instructions provided in-clinic on 2 occasions, and telephone support on 2 additional, interim occasions. The physical exercise program is intended to enhance fitness levels, in general, and to improve thermoregulation specifically related to hot flushes. Group AB will receive both the CBT and exercise program elements. Women allocated to the intervention groups will be asked to complete a battery of questionnaires assessing menopausal symptoms (the primary outcome), sexuality, body- and self-image, psychological distress and generic HRQL prior to the start of the program (baseline, T0), at 12 weeks (T1) and at 6 months follow-up (T2). Women allocated to the control group will complete the same questionnaire battery at parallel points in time.

Results/ relevance: If demonstrated to be effective, the availability of a structured supportive intervention program (modules A, B or AB) will be a welcome addition to regular medical care offered to breast cancer patients with treatment-induced menopause. It is anticipated that such a program will have direct benefit in terms of symptoms relief and the improvement of patients' HRQL.


Options:
A: Inclusion Criteria:

* Postmenopausal women (defined as the surgical or natural absence of menstrual cycles for at least 1 year prior to breast cancer diagnosis).
* 75 years or younger
* AJCC Stages I-IIIC Breast Cancer
* Taking an AI for at least 2 months
* Currently experiencing at least mild arthralgia (= or \> 3 on the BPI) associated with AI use
* Physically able to exercise and physician consent to start an exercise program
* Sedentary activity pattern (\< 90 mins/week of moderate-to-vigorous intensity sports activity) within the past year and low fitness level
* No more than one strength training session per week within the past year
* Agrees to be randomly assigned to either exercise or attention control
* Gives informed consent to participate in all study activities
* Able to come for baseline, 6-, and 12-month clinic visits and strength training sessions (6-month intervention study - able to come for baseline, 6-month clinic visits and strength training sessions).
* Mentally competent

Exclusion Criteria:

* Lymphedema with self reported 'flare up' in the past 4 months
B: Inclusion Criteria:

The study sample will be composed of 325 women, younger than 50 years of age, with histologically confirmed primary breast cancer (stages: T1 - T4, N0 - N1 and M0). All women will have been premenopausal at the time of diagnosis, have completed adjuvant chemotherapy (with the exception of herceptin, which can continue to receive) a minimum of 4 months and a maximum of 5 years prior to study entry. Women may currently be receiving adjuvant hormonal therapy. All women should be disease-free at time of study entry. Potentially eligible women will be screened for the presence of at least one of the following 3 menopausal symptoms during the previous 2-month period: hot flushes, sweating and/or vaginal dryness.

Exclusion Criteria:

Women will be excluded from the study if they lack basic proficiency in Dutch, if they have serious cognitive or psychiatric problems, or serious physical comorbidity that would preclude them from participating in a physical exercise program. Since physical exercise may be contraindicated as a treatment for hot flushes in obese women, 49 patients with a BMI ≥ 30 will be excluded from the study. Patients participating in concurrent studies or rehabilitation programs containing psychosocial interventions will also be excluded.
C: Inclusion Criteria:

* Female, 30 to 70 years of age, with first diagnosis of ductal carcinoma in situ (DCIS) or Stage I or Stage II breast cancer
* If chemotherapy or radiation therapy was received, the patient must be at least 4 weeks status post final primary treatment administration to allow treatment related cytokine changes to resolve. The participant may be taking longer term therapies such as aromatase inhibitors, estrogen receptor modulators, etc.
* If the patient has undergone a surgical procedure, she must be at least 8 weeks post-procedure.
* English speaking
* Medical clearance for participation provided by primary care physician or oncologist
* Postmenopausal
* Average fatigue over the past week of ≥ 3 on a 1 to 10 Likert scale or sleep dysfunction ≥ 1 on a 0 to 3 Likert scale
* Participating, on average, in no more than 20 minutes of physical activity on two or fewer days per week during the past six months
* Willing to abstain from "as needed" medications for 7 days prior to each blood draw. "As needed" medications are defined as any medicine (prescription or over-the-counter) that is taken sporadically as needed for specific complaints rather than taken at regularly scheduled intervals (e.g., daily).

Exclusion Criteria:

* Metastatic or recurrent breast cancer
* Inability to ambulate without assistance
* Unstable angina
* New York Heart Association class II, III, or IV congestive heart failure
* Uncontrolled asthma
* Interstitial lung disease
* Current use of steroids
* Having been told by a physician to only do exercise prescribed by a physician
* Dementia or organic brain syndrome
* Schizophrenia or active psychosis
* Connective tissue or rheumatologic disease \[i.e., Systemic lupus erythematosus, rheumatoid arthritis, amyloidosis, Reiter's syndrome, psoriatic arthritis, mixed connective tissue disease, Sjögren's syndrome, progressive systemic sclerosis, CREST syndrome, polymyositis, dermatomyositis, vasculitis, polymyalgia rheumatic, temporal arteritis\]
* Anticipates undergoing elective surgery during the duration of the intervention which would interfere with intervention participation (e.g., breast reconstructive surgery).
* Do not live or work less than 50 miles from the study site
* Lack of transportation to the study site
* Changes in usual medications expected during the study time period
* Plan to move residence out of the local area during the 5 months of the study
* Plan to travel out of the local area for vacation during the first 4 weeks of the intervention or plan to travel out of the local area for more than a week during the last 8 weeks of the intervention
* Contraindication to participation in physical activity (i.e., moderate intensity walking and strength training with resistance bands)
D: Inclusion Criteria:

* Female breast cancer patients between the ages of 18 and 70 years of age with a diagnosis of ductal carcinoma in situ (DCIS) or Stage I, II, or IIIA breast cancer and who are not currently receiving (and do not plan to receive during the duration of the study) chemotherapy or radiation therapy. The participant may be taking longer term therapies such as aromatase inhibitors, estrogen receptor modulators, etc. The upper age limit of 70 years was chosen to reduce the likelihood of adverse events or study drop-out due to increasing comorbidities (e.g., cardiovascular disease) that occur with age.
* If the patient has undergone a surgical procedure, enrollment will be delayed until ≥ 8 weeks post-procedure.
* English speaking.
* Medical clearance for participation provided by primary care physician or oncologist.
* Participating, on average, in no more than 60 minutes of moderate physical activity or no more than 30 minutes of vigorous activity per week during the past six months.

Exclusion Criteria:

* Diagnosis of dementia or organic brain syndrome.
* Medical, psychological, or social characteristic that would interfere with ability to fully participate in program activities and assessments (e.g., psychosis, schizophrenia, etc.).
* Contraindication to participation in a regular physical activity program.
* Metastatic or recurrent disease.
* Inability to ambulate.
* Anticipates undergoing elective surgery during the duration of the intervention which would interfere with intervention participation (e.g., breast reconstructive surgery).
* Planned travel that would interfere with scheduled study sessions (no travel in the 1st 4 months and no travel ≥ 1 week in the last 8 weeks of the intervention).

Answer: B