Breast Cancer, Other Disorders of Bone Density and Structure
Conditions
Brief summary
The purpose of this study is to identify the combined impact on bone loss as well as the incidence of bone fractures in women with estrogen receptor (ER)-positive, early breast cancer treated with an aromatase inhibitor (AI) either as first line therapy or as maintenance therapy after initial treatment with chemotherapy, in real life clinical settings in Greece.
Detailed description
Subjects with ER-positive early breast cancer will be treated with AIs either as first line therapy or as maintenance therapy after initial treatment with chemotherapy. The total study duration will be 24 months comprising of a recruitment period of 12 months and a follow-up period of 12 months for each participating subject. The primary outcome variable is the mean percentage variation in lumbar spine (LS) bone mineral density (BMD) during the 12 month follow - up period. Measurements will be taken before and after chemotherapy and at the end of the 12 month follow - up period.
Interventions
DRUGChemotherapy
Sponsors
Hellenic Breast Surgeons Society
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Provision of informed consent. * Age ≥ 40 years. * Female patients with ER-positive early breast cancer, who receive therapy with a third generation AI either as first line hormonal treatment or as maintenance therapy after first-line anthracycline- and/or taxane-based chemotherapy for a period no longer than 1 month (4 weeks) prior to inclusion in the present study. * Women who have been rendered postmenopausal prior to chemotherapy commencement and at least 12 months from last menstrual period. For subjects who are amenorrheic for \< 12 months (including patients who underwent hysterectomy, or received estrogen replacement therapy (ERT)/ hormone replacement therapy (HRT), they must have serum follicle stimulating hormone (FSH) ≥50 IU/L before the commencement of AI therapy. * Patients with available data on lumbar spine and total hip bone mineral density (BMD) prior to chemotherapy initiation as well as before the commencement of AI therapy.
Exclusion criteria
* Prior administration of other endocrine therapy including tamoxifen. * Chemotherapy-induced menopause. * Evidence of diseases known to interfere with bone metabolism, such as hyperparathyroidism, hyperthyroidism, osteomalacia, chronic liver disease, renal failure, hypercortisolism, malabsorption, and immobilization. * Evidence of bone metastasis or evidence of abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator. * Involvement in the planning and conduct of the study. * Participation in other clinical study within a period of 3 months prior to any study related procedures. * Patients with normal bone density or mild osteopenia (T score \>= -2 in any site) under treatment with oral or intravenous bisphosphonates. Vitamin D and calcium supplements are allowed. * Patients with severe osteopenia or osteoporosis (T score \<= -2 in any site) under treatment with intravenous bisphosphonates. Oral bisphosphonates, Vitamin D and calcium supplements are allowed. * Patients under treatment with oral or intravenous bisphosphonates before chemotherapy commencement. * Patients that stopped hormone-replacement therapy (HRT) less than 3 months before chemotherapy commencement. * Patients that received neo-adjuvant treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Month 12 of AI Therapy | Baseline and month 13-18 (1-6 months of chemotherapy + 12 months of AI therapy) | BMD was evaluated at lumbar spine (LS) and hip (HIP) with measurements taken before CT, before AI therapy and at the end of the 12 month followup period while on AI treatment. Dual Energy X-Ray Absorptiometry (DEXA scan) was used with all measurements performed with the Explorer absorptiometer produced by Hologic, Bedford, MA, USA in the same referral site in Athens, apart from two centres in other cities which used however the same absorptiometer model with identical software. The primary outcome variable was the mean percentage change in LS BMD between the pre CT treatment measurement and the post 12 months AI measurements in the CT cohort. The HT cohort was included as a control group. |
Secondary
| Measure | Time frame |
|---|---|
| Percentage Change in Total Hip Bone Mineral Density From Baseline to Month 12 of AI Therapy. | Baseline and month 13-18 (1-6 months of chemotherapy + 12 months of AI therapy) |
| Percentage Change in Total Hip Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy | From AI commencement to month 12 of AI therapy |
| Percentage Change in Lumbar Spine Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy | From AI commencement to month 12 of AI therapy |
| Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Chemotherapy Completion | Baseline and month 1-6 (depending on duration of chemotherapy) |
| Mean Percentage Change in Lumbar Spine Bone Mineral Density From AI Commencement to Month 12 of Therapy. | Month 1-6 (depending on duration of chemotherapy) and month 13-18 |
| Bone Fracture Rate | During the 12 months of AI Therapy |
Countries
Greece
Participant flow
Recruitment details
A total of 290 post-menopausal female patients with ER-positive early breast cancer (BC) entered the study between February 2011 and December 2012. All 12 participating centers are hospitals where members of the Hellenic Society of Breast Surgeons operate.
Participants by arm
| Arm | Count |
|---|---|
| CT Cohort Patients were treated with a third generation AI, as subsequent endocrine therapy after initial treatment with chemotherapy (CT cohort), and were followed up for a 12-month period. | 86 |
| HT Cohort Patients were treated with a third generation AI, as adjuvant therapy (HT cohort) and were followed up for a 12-month period. | 123 |
| Total | 209 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not provide 12month BMD measurements | 38 | 43 |
Baseline characteristics
| Characteristic | Total | CT Cohort | HT Cohort |
|---|---|---|---|
| 1st degree relative with osteoporosis No | 187 participants | 79 participants | 108 participants |
| 1st degree relative with osteoporosis Yes | 22 participants | 7 participants | 15 participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 85 Participants | 25 Participants | 60 Participants |
| Age, Categorical Between 18 and 65 years | 124 Participants | 61 Participants | 63 Participants |
| Age, Continuous | 63.9 years STANDARD_DEVIATION 9.1 | 61.3 years STANDARD_DEVIATION 8.9 | 65.8 years STANDARD_DEVIATION 9.2 |
| BMI | 29.4 kg/m^2 STANDARD_DEVIATION 5.3 | 29.6 kg/m^2 STANDARD_DEVIATION 5.4 | 29.3 kg/m^2 STANDARD_DEVIATION 5.3 |
| Fracture History No | 186 participants | 76 participants | 110 participants |
| Fracture History Yes | 23 participants | 10 participants | 13 participants |
| Number of fractures in the past | 1.2 fractures STANDARD_DEVIATION 0.4 | 1.2 fractures STANDARD_DEVIATION 0.4 | 1.2 fractures STANDARD_DEVIATION 0.4 |
| Orthopedic Surgery No | 195 participants | 81 participants | 114 participants |
| Orthopedic Surgery Yes | 14 participants | 5 participants | 9 participants |
| Osteopenia/osteoporosis before AI start Absent | 159 participants | 70 participants | 89 participants |
| Osteopenia/osteoporosis before AI start Present | 50 participants | 16 participants | 34 participants |
| Physical Exercise No | 175 participants | 74 participants | 101 participants |
| Physical Exercise Yes | 34 participants | 12 participants | 22 participants |
| Sex: Female, Male Female | 209 Participants | 86 Participants | 123 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Smoker Current smoker | 41 participants | 20 participants | 21 participants |
| Smoker Ex smoker | 23 participants | 14 participants | 9 participants |
| Smoker Non smoker | 145 participants | 52 participants | 93 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 123 |
| serious Total, serious adverse events | 0 / 86 | 0 / 123 |
Outcome results
Primary
Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Month 12 of AI Therapy
BMD was evaluated at lumbar spine (LS) and hip (HIP) with measurements taken before CT, before AI therapy and at the end of the 12 month followup period while on AI treatment. Dual Energy X-Ray Absorptiometry (DEXA scan) was used with all measurements performed with the Explorer absorptiometer produced by Hologic, Bedford, MA, USA in the same referral site in Athens, apart from two centres in other cities which used however the same absorptiometer model with identical software. The primary outcome variable was the mean percentage change in LS BMD between the pre CT treatment measurement and the post 12 months AI measurements in the CT cohort. The HT cohort was included as a control group.
Time frame: Baseline and month 13-18 (1-6 months of chemotherapy + 12 months of AI therapy)
Population: Patients with LS BMd measurements both at baseline and at 12 months of AI therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CT Cohort | Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Month 12 of AI Therapy | -0.72 percentage of change |
Secondary
Bone Fracture Rate
Time frame: During the 12 months of AI Therapy
Population: All patients with available 12 month follow-up during AI treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CT Cohort | Bone Fracture Rate | 0 participants |
| HT Cohort | Bone Fracture Rate | 0 participants |
Secondary
Mean Percentage Change in Lumbar Spine Bone Mineral Density From AI Commencement to Month 12 of Therapy.
Time frame: Month 1-6 (depending on duration of chemotherapy) and month 13-18
Population: Patients with LS BMD measurements both at AI commencement and at 12 months of AI therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CT Cohort | Mean Percentage Change in Lumbar Spine Bone Mineral Density From AI Commencement to Month 12 of Therapy. | -0.59 percentage of change |
Secondary
Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Chemotherapy Completion
Time frame: Baseline and month 1-6 (depending on duration of chemotherapy)
Population: Patients with LS BMD measurements both at baseline (before chemotherapy commencement) and at chemotherapy completion
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CT Cohort | Mean Percentage Change in Lumbar Spine Bone Mineral Density From Baseline (Before Chemotherapy Commencement) to Chemotherapy Completion | -0.19 percentage of change |
Secondary
Percentage Change in Lumbar Spine Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy
Time frame: From AI commencement to month 12 of AI therapy
Population: Patients with LS BMD measurements both at AI commencement and at 12 months of AI therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HT Cohort | Percentage Change in Lumbar Spine Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy | 1.51 percentage of change |
Secondary
Percentage Change in Total Hip Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy
Time frame: From AI commencement to month 12 of AI therapy
Population: Patients with HIP BMD measurements both at AI commencement and at 12 months of AI therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HT Cohort | Percentage Change in Total Hip Bone Mineral Density Before AI Commencement to Month 12 of Therapy for Patients Who Are Treated With AIs as First Line Therapy | -0.94 percentage of change |
Secondary
Percentage Change in Total Hip Bone Mineral Density From Baseline to Month 12 of AI Therapy.
Time frame: Baseline and month 13-18 (1-6 months of chemotherapy + 12 months of AI therapy)
Population: Patients with HIP BMD measurements both at baseline and at 12 months of AI therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CT Cohort | Percentage Change in Total Hip Bone Mineral Density From Baseline to Month 12 of AI Therapy. | 0.83 percentage of change |