Pilot Study to Evaluate the Effect of Aromatase Inhibitor Therapy on Pain Threshold in Breast Cancer Patients

Prospective Pilot Study to Determine the Effect of Aromatase Inhibitor-induced Estrogen Depletion on Evoked Pain Threshold and Psychosocial Factors in Breast Cancer Patients

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.

Study Overview

• Status: Completed
• Conditions: Pain; Breast Cancer; Arthralgia
• Intervention / Treatment: Drug: Anastrozole; Drug: exemestane; Drug: letrozole

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Postmenopausal women with ER positive early stage breast cancer who are starting AI therapy

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	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: Arimidex; Drug: exemestane; 25 mg orally daily; Other Names: Aromasin; Drug: letrozole; 2.5 mg orally daily; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, 3 months, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline patient-reported outcomes measures, 6 month persistence with therapy
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.	Baseline, 3 months

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Damon Runyon Cancer Research Foundation
• Investigators: Principal Investigator: Norah L Henry, MD, PhD, University of Michigan Rogel Cancer Center

Publications and helpful links

General Publications

• Henry NL, Conlon A, Kidwell KM, Griffith K, Smerage JB, Schott AF, Hayes DF, Williams DA, Clauw DJ, Harte SE. Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer. J Pain. 2014 May;15(5):468-75. doi: 10.1016/j.jpain.2014.01.487. Epub 2014 Jan 22.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: March 15, 2013
• First Submitted That Met QC Criteria: March 15, 2013
• First Posted (Estimated): March 19, 2013

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 15, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Pain threshold; Aromatase inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Joint Diseases; Musculoskeletal Diseases; Breast Neoplasms; Arthralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Anastrozole; Exemestane
• Other Study ID Numbers: UMCC 2008.101; HUM00026034 (Other Identifier: University of Michigan Comprehensive Cancer Center)