Arthralgia, Breast Cancer, Obesity
Conditions
Keywords
Joint pain, Grip strength, Hormone receptor positive breast cancer
Brief summary
Early stage hormone receptor positive breast cancer is typically treated with adjuvant endocrine therapy in order to decrease risk of breast cancer recurrence and to improve overall survival from the disease. Typical agents used for treatment include tamoxifen and the aromatase inhibitors. In postmenopausal women, aromatase inhibitor therapy is increasingly common because it is associated with fewer long-term serious toxicities compared to tamoxifen. However, aromatase inhibitors cause arthralgias in 40-50% of patients, which can influence adherence to therapy and can lead to treatment discontinuation in a minority of cases. The mechanism underlying development of this toxicity remains unclear, and predictors of who will develop these symptoms remain undefined. Initial reports suggest that grip strength decreases during aromatase inhibitor therapy, and that body-mass index may influence development of this symptom. Therefore, this longitudinal study has been developed to determine change in grip strength over time in women treated with aromatase inhibitors and tamoxifen, as well as to identify potential associations between change in grip strength and BMI. Patient self-reported symptoms will also be collected. A total of 115 women with early stage breast cancer who are initiating therapy with either an aromatase inhibitor or tamoxifen will be enrolled.
Interventions
DRUGanastrozole, letrozole, exemestane
Patients were treated with one of the listed anti-hormonal medications for up to one year
DRUGTamoxifen
Patients were treated with tamoxifen for up to one year
Sponsors
University of Michigan Rogel Cancer Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage 0-III breast cancer who are scheduled to receive endocrine therapy with tamoxifen or an aromatase inhibitor * All prior surgery and chemotherapy should be complete * Age 18 and above and postmenopausal
Exclusion criteria
* Major rheumatologic disorders * Concomitant sex hormone containing drugs or Leutinizing Hormone Releasing Hormone agonist therapy * For those subjects initiating treatment with an aromatase inhibitor, prior tamoxifen within 4 weeks of enrollment * For those subjects initiating treatment with tamoxifen, prior aromatase inhibitor within 4 weeks of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Change in Body Mass Index on Change in Grip Strength With Aromatase Inhibitor Therapy | baseline and 12 months | Change in BMI between baseline and 12 months of endocrine therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Medication on Change in Grip Strength | baseline and 12 months | Effect of either aromatase inhibitor or tamoxifen therapy on change in grip strength between baseline and 12 months |
| Association Between Baseline Body Mass Index and Discontinuation of Aromatase Inhibitor Therapy Within the First 12 Months | baseline and 12 months | Associations between baseline BMI and whether or not aromatase inhibitor-treated patients discontinued treatment by 12 months. In the original statistical analysis plan, it was only intended to examine the association with aromatase inhibitor-treated patients, and not tamoxifen-treated patients. The numbers below reflect the number of patients in each group who discontinued initial endocrine therapy within the first 12 months of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AI Therapy Subjects who started treatment with any of the three aromatase inhibitor (AI) medications | 93 |
| Tamoxifen Subjects who started treatment with tamoxifen | 22 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 37 | 2 |
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | AI Therapy | Tamoxifen | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 61.5 years | 62 years |
| Average pain | 2.3 units on a scale STANDARD_DEVIATION 2.1 | 2.4 units on a scale STANDARD_DEVIATION 1.9 | 2.3 units on a scale STANDARD_DEVIATION 2.1 |
| Body-mass index | 30.4 kg/m^2 STANDARD_DEVIATION 7.1 | 29 kg/m^2 STANDARD_DEVIATION 7 | 30.1 kg/m^2 STANDARD_DEVIATION 7.1 |
| Maximum grip strength, left hand | 54.8 kPa STANDARD_DEVIATION 10.9 | 53.7 kPa STANDARD_DEVIATION 10.7 | 54.6 kPa STANDARD_DEVIATION 10.8 |
| Maximum grip strength, right hand | 57.5 kPa STANDARD_DEVIATION 11.7 | 56.4 kPa STANDARD_DEVIATION 10.9 | 57.3 kPa STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 93 Participants | 22 Participants | 115 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Waist-hip ratio | 0.91 ratio STANDARD_DEVIATION 0.09 | 0.92 ratio STANDARD_DEVIATION 0.12 | 0.91 ratio STANDARD_DEVIATION 0.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 37 / 93 | 2 / 22 |
| serious Total, serious adverse events | 1 / 93 | 0 / 22 |
Outcome results
Primary
Effect of Change in Body Mass Index on Change in Grip Strength With Aromatase Inhibitor Therapy
Change in BMI between baseline and 12 months of endocrine therapy
Time frame: baseline and 12 months
Population: These data only include patients who completed a full 12 months of treatment with either an aromatase inhibitor or tamoxifen and had grip strength data at both baseline and 12 months. Patients could have switched from one aromatase inhibitor to another. Those patients who discontinued treatment prior to the 12 month period were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AI Therapy | Effect of Change in Body Mass Index on Change in Grip Strength With Aromatase Inhibitor Therapy | -0.15 kg/m^2 | Standard Deviation 5.7 |
| Tamoxifen | Effect of Change in Body Mass Index on Change in Grip Strength With Aromatase Inhibitor Therapy | 2.44 kg/m^2 | Standard Deviation 6.11 |
Comparison: Compare difference in change in body mass index between baseline and 12 months between aromatase inhibitor- and tamoxifen-treated patientsp-value: 0.03Wilcoxon (Mann-Whitney)
Comparison: Examine association between change in body mass index and change in grip strength with aromatase inhibitor therapy. For the primary outcome, linear regression was used for analysis with change of grip strength as response variable. In the original statistical analysis plan only aromatase inhibitor-treated patients were to be included in this analysis. This analysis was not performed on the tamoxifen group because it isn't clinically relevant.p-value: 0.4262Regression, Linear
Secondary
Association Between Baseline Body Mass Index and Discontinuation of Aromatase Inhibitor Therapy Within the First 12 Months
Associations between baseline BMI and whether or not aromatase inhibitor-treated patients discontinued treatment by 12 months. In the original statistical analysis plan, it was only intended to examine the association with aromatase inhibitor-treated patients, and not tamoxifen-treated patients. The numbers below reflect the number of patients in each group who discontinued initial endocrine therapy within the first 12 months of treatment
Time frame: baseline and 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AI Therapy | Association Between Baseline Body Mass Index and Discontinuation of Aromatase Inhibitor Therapy Within the First 12 Months | 37 participants |
| Tamoxifen | Association Between Baseline Body Mass Index and Discontinuation of Aromatase Inhibitor Therapy Within the First 12 Months | 2 participants |
Comparison: Association between baseline body mass index and discontinuation of aromatase inhibitor therapy. The original statistical analysis plan only called for analyzing the aromatase inhibitor-treated patients, not the tamoxifen-treated patients.95% CI: [0.92, 1.04]
Secondary
Effect of Medication on Change in Grip Strength
Effect of either aromatase inhibitor or tamoxifen therapy on change in grip strength between baseline and 12 months
Time frame: baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AI Therapy | Effect of Medication on Change in Grip Strength | -7.0 percent change | Standard Deviation 15.9 |
| Tamoxifen | Effect of Medication on Change in Grip Strength | 0.6 percent change | Standard Deviation 10.2 |
Comparison: Comparison of change in maximum grip strength between baseline and 12 months for aromatase inhibitor-treated versus tamoxifen-treated patientsp-value: 0.032Wilcoxon (Mann-Whitney)