Effects of Aromatase Inhibitor Therapy on Muscle Function

A Pilot Study Examining Molecular and Clinical Effects of Aromatase Inhibitor Therapy on Skeletal Muscle Function in Early Stage Breast Cancer

This is a pilot study designed to examine changes in muscle function after Aromatase Inhibitor (AI) therapy, at both the molecular and clinical level.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Breast Cancer Female

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Iu Simon Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Post menopausal women with non metastatic breast cancer planning to initiate aromatase inhibitor therapy at the IU Simon Cancer Center oncology clinic.

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Post-menopausal
3. Diagnosis of ductal carcinoma in situ (DCIS) or stage I, II, or III ER positive breast cancer
4. Plan to initiate an AI per treating physician.
5. Completion of all primary therapy for breast cancer, including surgery, radiation, and chemotherapy (should be completed 14 days or more prior to obtaining the baseline muscle biopsy). Ongoing HER2 targeted therapy with trastuzumab and/or pertuzumab is allowed. Ongoing neratinib therapy is not allowed.
6. Body weight less than 350 lbs., as dictated by the weight limit for DXA (dual energy x-ray absorptiometry) scanner
7. Must be willing to undergo muscle biopsy at baseline and after 24 weeks of AI therapy
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at the time of study enrollment
9. Informed consent and authorization of the release of health information must be obtained according to institutional guidelines

Exclusion Criteria:

1. Unwilling to co-enroll into the FIT core study
2. Diagnosis of severe osteopenia or osteoporosis, defined as a bone mineral density of ≥ 2.0 standard deviations below the young adult female reference mean (T score)
3. Diagnosis of other disorder affecting bone function or turnover, such as Paget's disease, renal osteodystrophy, parathyroid disorders, or vitamin D deficiency/osteomalacia
4. Prior history of non-traumatic, fragility bone fracture
5. Any muscle or neuromuscular disorder affecting muscle function, such as muscular dystrophy, myositis, or amyotrophic lateral sclerosis
6. Any condition precluding power protocol participation (i.e. exertion on a stationary bicycle), including: New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, myocardial infarction in the prior 12 months, orthopedic surgery in the previous 6 months or plans for orthopedic surgery during the study period, chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms > 2 days/week) or dyspnea requiring oxygen, symptomatic peripheral vascular disease, or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator
7. Need for daily anticoagulation use
8. Allergy to local anesthetic
9. Locally recurrent or metastatic breast cancer a. History of prior treated malignancies, other than breast cancer, that are now stable, are in remission, and do not require active therapy, are acceptable.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in calstabin1 binding to RyR1 channels in skeletal muscle	Changes in calstabin1 binding to RyR1 channels in skeletal muscle of breast cancer patients pre and post exposure to adjuvant aromatase inhibitor therapy	through day 168 of aromatase inhibitor therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in ryanodine receptor/calcium release channel (RyR1) oxidation in skeletal muscle	To estimate changes in RyR1 oxidation in skeletal muscle of breast cancer patients, pre- and post- exposure to adjuvant aromatase inhibitor therapy	through day 168 of aromatase inhibitor therapy
Relationship between changes in RyR1 biochemistry and measures of muscle function	To explore the relationship between changes in RyR1 biochemistry and measures of muscle function, including muscle power as measured by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Relationship between markers of bone turnover and changes in RyR1 biochemistry	To explore the relationship between markers of bone turnover and changes in RyR1 biochemistry (calstabin binding to RyR1)	through day 168 of aromatase inhibitor therapy
Relationship between markers of bone turnover and changes in muscle function	To explore the relationship between markers of bone turnover and changes in muscle function in terms of muscle power assessed by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy	To better characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy, in terms muscle power measured by isokinetic dynamometry	through day 168 of aromatase inhibitor therapy
Feasibility of repeated muscle biopsies in patients with early stage breast cancer initiating aromatase inhibitor therapy	5. To describe the feasibility of repeated muscle biopsies in patients with early stage breast cancer initiating aromatase inhibitor therapy, in terms of rate of completion of baseline and follow up biopsy	through day 168 of aromatase inhibitor therapy

Collaborators and Investigators

• Sponsor: Tarah J Ballinger, MD

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2018
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): February 7, 2020

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: June 26, 2018
• First Posted (Actual): July 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 10, 2021
• Last Update Submitted That Met QC Criteria: May 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer; ER positive; Post Menopausal; Aromatase Inhibitor Therapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IUSCC-0647

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No