Pilot Study to Evaluate the Effect of Aromatase Inhibitor Therapy on Pain Threshold in Breast Cancer Patients
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Women starting AI therapy There is only a single cohort. Postmenopausal women with ER 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. |
Drug: Anastrozole
1 mg orally daily
Other Names:
Drug: exemestane
25 mg orally daily
Other Names:
Drug: letrozole
2.5 mg orally daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- Lynn Henry
- Damon Runyon Cancer Research Foundation
Investigators
- Principal Investigator: Norah L Henry, MD, PhD, University of Michigan Rogel Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- UMCC 2008.101
- HUM00026034
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Women Starting AI Therapy |
|---|---|
| Arm/Group Description | There is only a single cohort. Postmenopausal women with hormone 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. |
| Period Title: Overall Study | |
| STARTED | 50 |
| 3 Month Evaluation | 43 |
| COMPLETED | 36 |
| NOT COMPLETED | 14 |
Baseline Characteristics
| Arm/Group Title | Women Starting Aromatase Inhibitor (AI) Therapy |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 50 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
60
|
| Sex: Female, Male (Count of Participants) | |
| Female |
50
100%
|
| Male |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
4%
|
| White |
47
94%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Weight, kg (kilograms) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kilograms] |
80.7
(17.8)
|
| Body mass index (kg/m^2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/m^2] |
30.0
(6.5)
|
| Aromatase inhibitor (participants) [Number] | |
| anastrozole 1 mg daily |
40
80%
|
| exemestane 25 mg daily |
1
2%
|
| letrozole 2.5 mg daily |
9
18%
|
| Prior chemotherapy (participants) [Number] | |
| prior chemotherapy |
23
46%
|
| no prior chemotherapy |
27
54%
|
| Prior tamoxifen (participants) [Number] | |
| prior tamoxifen |
14
28%
|
| no prior tamoxifen |
36
72%
|
| Mean Pain50, kg/cm^2 (kg/cm^2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/cm^2] |
4.3
(1.5)
|
| Mean conditioned pain modulation (CPM) (units on a scale (0-100 pain scale)) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [units on a scale (0-100 pain scale)] |
7.9
(14.7)
|
| Mean serum estradiol, pg/ml (pg/ml) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [pg/ml] |
6.0
(7.6)
|
Outcome Measures
| Title | Mean Pain50 Assessed at Baseline, 3 Months and 6 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Women Starting AI Therapy |
|---|---|
| Arm/Group Description | There is only a single cohort. Postmenopausal women with ER 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. |
| Measure Participants | 50 |
| Baseline |
4.3
(1.5)
|
| 3 month |
4.2
(1.8)
|
| 6 month |
4.2
(1.6)
|
| Title | Mean Conditioned Pain Modulation Assessed at Baseline, 3 Months, and 6 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Women Starting AI Therapy |
|---|---|
| Arm/Group Description | There is only a single cohort. Postmenopausal women with ER 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. |
| Measure Participants | 50 |
| baseline |
7.9
(14.7)
|
| 3 months |
6.3
(18.4)
|
| 6 months |
10.4
(18.9)
|
| Title | Mean Baseline Patient-reported Symptom Measures for Patients Who Were Persistent and Nonpersistent With Aromatase Inhibitor Therapy During the First 6 Months of Treatment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Women Starting AI Therapy |
|---|---|
| Arm/Group Description | There is only a single cohort. Postmenopausal women with ER 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. |
| Measure Participants | 50 |
| Baseline depression, discontinuation by 6 mo |
14
(9.5)
|
| Baseline depression, no discontinuation by 6 mo |
6.6
(5.9)
|
| Baseline sleep, discontinuation by 6 mo |
47.1
(17.9)
|
| Baseline sleep, no discontinuation by 6 mo |
28.6
(17.8)
|
| BL general fatigue, discontinuation by 6 mo |
16.9
(3.6)
|
| BL general fatigue, no discontinuation by 6 mo |
10.6
(4.1)
|
| BL pain, discontinuation by 6 mo |
1.9
(1.2)
|
| Baseline pain, no discontinuation by 6 mo |
1.6
(1.3)
|
| Title | Estradiol Concentration Assessments at Baseline and After 3 Months of Aromatase Inhibitor Therapy |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Women Starting AI Therapy |
|---|---|
| Arm/Group Description | There is only a single cohort. Postmenopausal women with ER 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. |
| Measure Participants | 50 |
| Baseline |
6.0
(7.6)
|
| 3 months |
0.75
(0.45)
|
Adverse Events
| Time Frame | 6 months | |
|---|---|---|
| Adverse Event Reporting Description | We only collected data related to the study specific procedures, not the standard of care aromatase inhibitor medication. | |
| Arm/Group Title | Women Starting AI Therapy | |
| Arm/Group Description | There is only a single cohort. Postmenopausal women with ER 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. | |
All Cause Mortality |
||
| Women Starting AI Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Women Starting AI Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/50 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Women Starting AI Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/50 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Norah Lynn Henry |
|---|---|
| Organization | University of Michigan Comprehensive Cancer Center |
| Phone | 734-936-4991 |
| norahh@med.umich.edu |
- UMCC 2008.101
- HUM00026034