Arthralgia, Breast Cancer, Pain
Conditions
Keywords
Aromatase inhibitor, Pain threshold
Brief summary
Postmenopausal women who have hormone receptor positive breast cancer are typically treated with aromatase inhibitor medications, which substantially decrease the amount of estrogen produced by their bodies. These medications are fairly well tolerated, but can cause aches and pains which can be quite severe in some cases. People experience pain differently. Estrogen appears to play a role in how we experience pain. Therefore, decreasing estrogen levels may lead to more pain in some women than others. The goal of this study is to evaluate perception of pain in women with breast cancer, and to determine if differences in pain perception lead to more aches and pains in some women treated with aromatase inhibitors. In this study, we plan to enroll 55 women with breast cancer who are starting treatment with an aromatase inhibitor. Participants will undergo testing to evaluate their perception of pain, and will also complete a set of questionnaires. Testing will be conducted before starting aromatase inhibitor therapy, as well as after 3 and 6 months of therapy. We will investigate whether pre-existing differences in pain perception lead to different amounts of pain during aromatase inhibitor therapy.
Interventions
DRUGAnastrozole
1 mg orally daily
DRUGexemestane
25 mg orally daily
DRUGletrozole
2.5 mg orally daily
Sponsors
Damon Runyon Cancer Research Foundation
University of Michigan Rogel Cancer Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female gender * Postmenopausal, age 21 or greater * Stage 0-III estrogen receptor and/or progesterone receptor positive breast cancer who will be receiving a standard dose of letrozole, anastrozole, or exemestane * Performance status 0-2 * Willing to sign the consent form
Exclusion criteria
* Average pain \>=8/10 over the past 24 hours * Peripheral sensory neuropathy grade 2 or higher * Personal history of schizophrenia, or suicidal ideation or attempt within the past 2 years * Thumbnail abnormalities on either hand that are likely to alter pain perception during testing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Pain50 Assessed at Baseline, 3 Months and 6 Months | Baseline, 3 months, 6 months | Patients rated the intensity of each pressure sensation using a 0 to 100 numerical rating scale (0 = no pain, 100 = worst pain imaginable). Pain50 was defined as the amount of applied pressure in kilograms per square centimeter that evoked a pain intensity rating of 50 out of 100. Pain50 was assessed at baseline, 3 months, and 6 months. Change in Pain50 with estrogen depletion was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months | Baseline, 3 months, 6 months | To assess conditioned pain modulation, pressure equivalent to the patient's Pain50 was applied to the non-dominant thumbnail for 30 seconds (test stimulus), and the patient rated the intensity of the pressure on a 0-100 pain scale at 10 second intervals. Ten minutes later pressure (conditioning stimulus) was continuously applied to the dominant thumbnail for 60 seconds at the same Pain50 intensity. After 30 seconds, the test stimulus was again applied to the non-dominant thumbnail for 30 seconds and the patient rated the intensity every 10 seconds. Conditioned pain modulation magnitude was calculated as the difference (second minus first) in the mean of the 3 pain ratings to the test stimulus applied prior to and during the conditioning stimulus. Conditioned pain modulation was assessed at baseline, 3 months, and 6 months. Change over that time period was assessed. Higher conditioned pain modulation values indicate less efficient conditioned pain modulation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline patient-reported outcomes measures, 6 month persistence with therapy | Patients completed 4 measures at baseline, before aromatase inhibitor therapy initiation. (1) Depression: Center for Epidemiologic Studies-Depression, scores 0-60, higher scores reflect more depression. (2) Pain: 7 day Pain Diary, scores 0-10, higher scores reflect more pain. (3) Fatigue: Multidimensional Fatigue Inventory, scores 4-20, higher scores reflect more fatigue. (4) Sleep: Medical Outcomes Study-Sleep, scores 0-100, higher scores reflect worse sleep. Persistence with aromatase inhibitor therapy was assessed at the 6 month timepoint. Mean baseline values for each measure were calculated for the cohort that persisted with aromatase inhibitor therapy and the cohort that was non-persistent. |
| Estradiol Concentration Assessments at Baseline and After 3 Months of Aromatase Inhibitor Therapy | Baseline, 3 months | Estradiol is being assessed using an ultrasensitive gas chromatography tandem mass spectroscopy-based assay. The lower limit of detection of the assay is 0.625 pg/ml. For patients whose serum estradiol concentrations were below the lower limit of detection, the value of 0.625 pg/ml was used to calculate the mean estradiol concentration and standard deviation at both baseline and 3 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Women Starting Aromatase Inhibitor (AI) Therapy There is only a single cohort. Postmenopausal women with estrogen receptor positive breast cancer who are starting treatment with anastrozole 1 mg daily, letrozole 2.5 mg daily, or exemestane 25 mg daily. Choice of therapy is at the discretion of the treating physician. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Women Starting Aromatase Inhibitor (AI) Therapy |
|---|---|
| Age, Continuous | 60 years |
| Aromatase inhibitor anastrozole 1 mg daily | 40 participants |
| Aromatase inhibitor exemestane 25 mg daily | 1 participants |
| Aromatase inhibitor letrozole 2.5 mg daily | 9 participants |
| Body mass index | 30.0 kg/m^2 STANDARD_DEVIATION 6.5 |
| Mean conditioned pain modulation (CPM) | 7.9 units on a scale (0-100 pain scale) STANDARD_DEVIATION 14.7 |
| Mean Pain50, kg/cm^2 | 4.3 kg/cm^2 STANDARD_DEVIATION 1.5 |
| Mean serum estradiol, pg/ml | 6.0 pg/ml STANDARD_DEVIATION 7.6 |
| Prior chemotherapy no prior chemotherapy | 27 participants |
| Prior chemotherapy prior chemotherapy | 23 participants |
| Prior tamoxifen no prior tamoxifen | 36 participants |
| Prior tamoxifen prior tamoxifen | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight, kg | 80.7 kilograms STANDARD_DEVIATION 17.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Mean Pain50 Assessed at Baseline, 3 Months and 6 Months
Patients rated the intensity of each pressure sensation using a 0 to 100 numerical rating scale (0 = no pain, 100 = worst pain imaginable). Pain50 was defined as the amount of applied pressure in kilograms per square centimeter that evoked a pain intensity rating of 50 out of 100. Pain50 was assessed at baseline, 3 months, and 6 months. Change in Pain50 with estrogen depletion was determined.
Time frame: Baseline, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Women Starting AI Therapy | Mean Pain50 Assessed at Baseline, 3 Months and 6 Months | Baseline | 4.3 kg/cm^2 | Standard Deviation 1.5 |
| Women Starting AI Therapy | Mean Pain50 Assessed at Baseline, 3 Months and 6 Months | 3 month | 4.2 kg/cm^2 | Standard Deviation 1.8 |
| Women Starting AI Therapy | Mean Pain50 Assessed at Baseline, 3 Months and 6 Months | 6 month | 4.2 kg/cm^2 | Standard Deviation 1.6 |
Secondary
Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months
To assess conditioned pain modulation, pressure equivalent to the patient's Pain50 was applied to the non-dominant thumbnail for 30 seconds (test stimulus), and the patient rated the intensity of the pressure on a 0-100 pain scale at 10 second intervals. Ten minutes later pressure (conditioning stimulus) was continuously applied to the dominant thumbnail for 60 seconds at the same Pain50 intensity. After 30 seconds, the test stimulus was again applied to the non-dominant thumbnail for 30 seconds and the patient rated the intensity every 10 seconds. Conditioned pain modulation magnitude was calculated as the difference (second minus first) in the mean of the 3 pain ratings to the test stimulus applied prior to and during the conditioning stimulus. Conditioned pain modulation was assessed at baseline, 3 months, and 6 months. Change over that time period was assessed. Higher conditioned pain modulation values indicate less efficient conditioned pain modulation.
Time frame: Baseline, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Women Starting AI Therapy | Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months | 6 months | 10.4 units on a scale (0-100 pain scale) | Standard Deviation 18.9 |
| Women Starting AI Therapy | Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months | baseline | 7.9 units on a scale (0-100 pain scale) | Standard Deviation 14.7 |
| Women Starting AI Therapy | Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months | 3 months | 6.3 units on a scale (0-100 pain scale) | Standard Deviation 18.4 |
Other Pre-specified
Estradiol Concentration Assessments at Baseline and After 3 Months of Aromatase Inhibitor Therapy
Estradiol is being assessed using an ultrasensitive gas chromatography tandem mass spectroscopy-based assay. The lower limit of detection of the assay is 0.625 pg/ml. For patients whose serum estradiol concentrations were below the lower limit of detection, the value of 0.625 pg/ml was used to calculate the mean estradiol concentration and standard deviation at both baseline and 3 months.
Time frame: Baseline, 3 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Women Starting AI Therapy | Estradiol Concentration Assessments at Baseline and After 3 Months of Aromatase Inhibitor Therapy | Baseline | 6.0 pg/ml | Standard Deviation 7.6 |
| Women Starting AI Therapy | Estradiol Concentration Assessments at Baseline and After 3 Months of Aromatase Inhibitor Therapy | 3 months | 0.75 pg/ml | Standard Deviation 0.45 |
Other Pre-specified
Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment
Patients completed 4 measures at baseline, before aromatase inhibitor therapy initiation. (1) Depression: Center for Epidemiologic Studies-Depression, scores 0-60, higher scores reflect more depression. (2) Pain: 7 day Pain Diary, scores 0-10, higher scores reflect more pain. (3) Fatigue: Multidimensional Fatigue Inventory, scores 4-20, higher scores reflect more fatigue. (4) Sleep: Medical Outcomes Study-Sleep, scores 0-100, higher scores reflect worse sleep. Persistence with aromatase inhibitor therapy was assessed at the 6 month timepoint. Mean baseline values for each measure were calculated for the cohort that persisted with aromatase inhibitor therapy and the cohort that was non-persistent.
Time frame: Baseline patient-reported outcomes measures, 6 month persistence with therapy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline sleep, no discontinuation by 6 mo | 28.6 units on a scale | Standard Deviation 17.8 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | BL general fatigue, no discontinuation by 6 mo | 10.6 units on a scale | Standard Deviation 4.1 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline depression, discontinuation by 6 mo | 14 units on a scale | Standard Deviation 9.5 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline depression, no discontinuation by 6 mo | 6.6 units on a scale | Standard Deviation 5.9 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline sleep, discontinuation by 6 mo | 47.1 units on a scale | Standard Deviation 17.9 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | BL general fatigue, discontinuation by 6 mo | 16.9 units on a scale | Standard Deviation 3.6 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | BL pain, discontinuation by 6 mo | 1.9 units on a scale | Standard Deviation 1.2 |
| Women Starting AI Therapy | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment | Baseline pain, no discontinuation by 6 mo | 1.6 units on a scale | Standard Deviation 1.3 |