Breast Cancer
Conditions
Keywords
estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer
Brief summary
RATIONALE: Studying samples of blood from patients with breast cancer in the laboratory may help doctors learn how well triptorelin given together with tamoxifen citrate or exemestane works in lowering estrogen levels. PURPOSE: This clinical trial is studying estrogen levels in premenopausal women who have undergone surgery for breast cancer and are receiving triptorelin and tamoxifen citrate or exemestane on clinical trial IBCSG-2402.
Detailed description
OBJECTIVES: Primary * Describe estrogen levels (estradiol \[E2\], estrone \[E1\], and estrone sulphate \[E1S\]) at different time points during the first 4 years of treatment with triptorelin in combination with either tamoxifen citrate or exemestane on clinical trial IBCSG-2402 in premenopausal women with resected breast cancer. * Assess whether there is a suboptimally estrogen-suppressed subgroup of patients who receive exemestane. Secondary * Compare estrogen levels (E2, E1, E1S) at different time points during treatment with triptorelin in combination with either tamoxifen citrate or exemestane. * Examine potential predictive factors of ineffective estrogen suppression (e.g., age, chemotherapy \[yes/no\], type of chemotherapy received, smoking history, BMI, and evidence of menses at study entry). * Investigate the predictive value of optimal estrogen suppression during the first 6 and 12 months of treatment with regard to long-term estrogen suppression (4-year period). * Compare disease-free survival of suboptimally estrogen-suppressed patients treated with exemestane with that of patients with optimal suppression (exploratory analysis). * Examine related endocrine function (FSH and LH) to further elucidate causes of suboptimal estrogen suppression. OUTLINE: This is a multicenter study. Blood samples are collected at baseline and at 3, 6, 12, 18, 24, 36, and 48 months for measurement of estrogen levels (estradiol \[E2\], estrone \[E1\], and estrone sulphate \[E1S\]) by gas chromatography-mass spectrometry and measurement of endocrine function (FSH and LH).
Interventions
OTHERgas chromatography / tandem mass spectometry
Determination of estrogen levels through gas chromatography.
Sponsors
ETOP IBCSG Partners Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
0 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed resected breast cancer * Concurrent enrollment on clinical trial IBCSG-2402 (SOFT trial) required * Randomized to receive triptorelin in combination with either tamoxifen citrate or exemestane * Hormone receptor status: * Estrogen receptor- and/or progesterone receptor-positive tumor PATIENT CHARACTERISTICS: * Premenopausal PRIOR CONCURRENT THERAPY: * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization | Estrogen levels (estradiol \[E2\], estrone \[E1\], and estrone sulphate \[E1S\]) were measured at the following time points for the SOFT-EST: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization. Some of these samples were not used, including un-scheduled sample, post surgery or vaginal bleeding, samples taken post early discontinuation (ED) or discontinuation of GnRH injections. |
| Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization | Suboptimal estrogen suppression (SES), estradiol (E2) levels greater than 2.72 pg/mL in at least 2 post-baseline samples. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline | The secondary analysis explored baseline estrogen levels (E2, E1, E1S) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm. |
| Comparison of Estrogen Levels at Different Time Points During Treatment | baseline (0 months), 3, 6, 12, 18, 24, 36, and 48 months from randomization | Percent (%) change of estrogen levels estradiol (E2), estrone (E1), and estrone sulphate (E1S) at each timepoint from baseline: e.g. {E2(t)-E2(0)} / E2(0)\*100, where t= 3, 6, 12, 18, 24, 36, and 48 months from randomization |
| Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Less than 12 months, at 12 months | Endocrine function (FSH, LH) status according to treatment assignments at 12 months using 12 month data alone or 12 month data plus earlier data (when 12 month not available) |
| Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline | The secondary analysis explored endocrine functions (FSH, LH) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm. |
| Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Four years after randomization | Potential predictive factors of ineffective estrogen suppression (SES) (with E2 \> 2.72 pg/mL, or any vaginal bleeding \> 3 months after triptorelin start or pregnancy) such as: age, evidence of menses at entry, BMI, chemotherapy (yes/no), and, type of chemotherapy received |
Countries
France, Hungary, Italy, Peru, Portugal, Spain, Sweden, Switzerland
Participant flow
Recruitment details
The SOFT-EST substudy was activated on 25 Nov 2008. Participating Centers were expected to enroll all or most patients who planned to use triptorelin as method of OFS, if randomized to receive OFS, into this substudy. The accrual goal for the substudy was 120 patients (30 T+OFS; 90 E+OFS). Enrollment of 30 patients randomly assigned to T+OFS was reached by 31 Dec 2009; enrollment of patients randomly assigned to E+OFS continued until SOFT and SOFT-EST enrollment closed on 31 Jan 2011.
Participants by arm
| Arm | Count |
|---|---|
| Triptorelin Plus Tamoxifen Determination of estrogen levels in blood samples from patients being treated with triptorelin plus tamoxifen for 5 years.
gas chromatography / tandem mass spectometry: Determination of estrogen levels through gas chromatography. | 26 |
| Triptorelin Plus Exemestane Determination of estrogen levels in blood samples from patients being treated with triptorelin plus exemestane for 5 years.
gas chromatography / tandem mass spectometry: Determination of estrogen levels through gas chromatography. | 83 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Baseline samples only, no sample analyzed or only single sample available | 6 | 8 |
Baseline characteristics
| Characteristic | Triptorelin Plus Tamoxifen | Triptorelin Plus Exemestane | Total |
|---|---|---|---|
| Age, Customized <35 | 0 Participants | 8 Participants | 8 Participants |
| Age, Customized 35-39 | 5 Participants | 10 Participants | 15 Participants |
| Age, Customized 40-44 | 7 Participants | 26 Participants | 33 Participants |
| Age, Customized 45-49 | 14 Participants | 39 Participants | 53 Participants |
| Estradiol (E2), pg/mL | 109.81 pg/mL STANDARD_DEVIATION 119.81 | 96.55 pg/mL STANDARD_DEVIATION 151.23 | 99.78 pg/mL STANDARD_DEVIATION 143.68 |
| Estrone (E1), pg/mL | 60.27 pg/mL STANDARD_DEVIATION 52.4 | 65.42 pg/mL STANDARD_DEVIATION 78.12 | 64.17 pg/mL STANDARD_DEVIATION 72.52 |
| Estrone sulfate (E1S), pg/mL | 1437.02 pg/mL STANDARD_DEVIATION 1825.06 | 1371.21 pg/mL STANDARD_DEVIATION 1763.84 | 1387.20 pg/mL STANDARD_DEVIATION 1770.42 |
| Follicle-stimulating hormone (FSH), LU/L | 25.14 LU/L STANDARD_DEVIATION 29.05 | 30.30 LU/L STANDARD_DEVIATION 27.37 | 29.05 LU/L STANDARD_DEVIATION 27.73 |
| Luteinizing hormone (LH), LU/L | 16.77 LU/L STANDARD_DEVIATION 16.29 | 18.97 LU/L STANDARD_DEVIATION 16.12 | 18.44 LU/L STANDARD_DEVIATION 16.11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 25 Participants | 81 Participants | 106 Participants |
| Sex: Female, Male Female | 26 Participants | 83 Participants | 109 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy
Estrogen levels (estradiol \[E2\], estrone \[E1\], and estrone sulphate \[E1S\]) were measured at the following time points for the SOFT-EST: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization. Some of these samples were not used, including un-scheduled sample, post surgery or vaginal bleeding, samples taken post early discontinuation (ED) or discontinuation of GnRH injections.
Time frame: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization
Population: The final (4 years) analysis cohort (N=109) consists of all patients from the intent to treat (ITT) population (N=123) who had at least 2 samples analyzed and who received at least one GnRH analogue triptorelin injection during follow-up. Fourteen patients were excluded due to the reasons of 1) never start TE and never received GnRH (gonadotropin-releasing hormone) analogue triptorelin; 2) only baseline sample available; 3) single sample at 24 months; 4) patients without sample analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 36 months | 3.704 pg/mL | Standard Deviation 2.138 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 3 months | 4.876 pg/mL | Standard Deviation 7.123 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 6 months | 3.761 pg/mL | Standard Deviation 2.02 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 12 months | 4.013 pg/mL | Standard Deviation 2.765 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 18 months | 7.306 pg/mL | Standard Deviation 16.325 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 24 months | 4.453 pg/mL | Standard Deviation 3.347 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at baseline (0 months) | 109.81 pg/mL | Standard Deviation 119.151 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 48 months | 5.914 pg/mL | Standard Deviation 8.959 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at baseline (0 months) | 60.27 pg/mL | Standard Deviation 52.4 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 3 months | 17.8 pg/mL | Standard Deviation 6.73 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 6 months | 18.66 pg/mL | Standard Deviation 7.54 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 12 months | 19.05 pg/mL | Standard Deviation 8.4 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 18 months | 18.64 pg/mL | Standard Deviation 9.35 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 24 months | 18.96 pg/mL | Standard Deviation 7.63 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 36 months | 19.49 pg/mL | Standard Deviation 7.32 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 48 months | 19.14 pg/mL | Standard Deviation 7.24 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at baseline (0 months) | 1437 pg/mL | Standard Deviation 1825.06 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 3 months | 281.4 pg/mL | Standard Deviation 183.44 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 6 months | 259 pg/mL | Standard Deviation 167.23 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 12 months | 278.5 pg/mL | Standard Deviation 236.38 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 18 months | 281.8 pg/mL | Standard Deviation 160.6 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 24 months | 242.6 pg/mL | Standard Deviation 96.75 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 36 months | 249.4 pg/mL | Standard Deviation 113.27 |
| Triptorelin Plus Tamoxifen | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 48 months | 231.1 pg/mL | Standard Deviation 93.46 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 36 months | 53.27 pg/mL | Standard Deviation 151.03 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at baseline (0 months) | 96.55 pg/mL | Standard Deviation 151.235 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 18 months | 8.47 pg/mL | Standard Deviation 33.42 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 3 months | 3.973 pg/mL | Standard Deviation 8.439 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 6 months | 54.7 pg/mL | Standard Deviation 97.66 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 6 months | 3.672 pg/mL | Standard Deviation 8.006 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 24 months | 4.69 pg/mL | Standard Deviation 9.16 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 12 months | 2.486 pg/mL | Standard Deviation 5 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 24 months | 73.56 pg/mL | Standard Deviation 258.29 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 18 months | 2.527 pg/mL | Standard Deviation 6.204 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 36 months | 4.93 pg/mL | Standard Deviation 9.16 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 24 months | 2.52 pg/mL | Standard Deviation 6.566 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 12 months | 47.31 pg/mL | Standard Deviation 130.45 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 36 months | 1.654 pg/mL | Standard Deviation 2.764 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 48 months | 8.53 pg/mL | Standard Deviation 35.07 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estradiol (E2) levels at 48 months | 9.073 pg/mL | Standard Deviation 57.307 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 48 months | 112 pg/mL | Standard Deviation 556.81 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at baseline (0 months) | 65.42 pg/mL | Standard Deviation 78.12 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at baseline (0 months) | 1371 pg/mL | Standard Deviation 1763.84 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 3 months | 2.93 pg/mL | Standard Deviation 3.33 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 18 months | 63.52 pg/mL | Standard Deviation 175.19 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 6 months | 2.73 pg/mL | Standard Deviation 3.12 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone sulfate (E1S) levels at 3 months | 56.02 pg/mL | Standard Deviation 133.71 |
| Triptorelin Plus Exemestane | Estrogen Levels (Estradiol [E2], Estrone [E1], and Estrone Sulphate [E1S]) at Different Time Points During the First 4 Years of Treatment With Triptorelin (Trip) in Combination With Either Tamoxifen (T) or Exemestane (E), IBCSG 24-02 SOFT-EST Substudy | Estrone (E1) levels at 12 months | 3.71 pg/mL | Standard Deviation 6.35 |
Primary
Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression
Suboptimal estrogen suppression (SES), estradiol (E2) levels greater than 2.72 pg/mL in at least 2 post-baseline samples.
Time frame: 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization
Population: Among patients randomly assigned to exemestane + triptorelin and included in the analysis cohort (N=83), the number of patients who experienced suboptimal suppression at each timepoint, with 95% exact binomial confidence intervals (CI), were reported. Two patients were excluded due to no baseline sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at baseline (0 months) | 74 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 3 months | 17 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 6 months | 16 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 12 months | 12 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 18 months | 12 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 24 months | 8 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 36 months | 8 Participants |
| Triptorelin Plus Tamoxifen | Number of Patients Who Receive Exemestane Experiencing Suboptimal Estrogen Suppression | Patients with E2 > 2.72 pg/mL at 48 months | 3 Participants |
Secondary
Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm
The secondary analysis explored endocrine functions (FSH, LH) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm.
Time frame: Baseline
Population: All patients from the Intent to treat (ITT) population assigned to exemestane +triptorelin (N=83) according to suboptimal estrogen suppression (SES) with E2 \> 2.72 pg/mL (suboptimal threshold) or any vaginal bleeding \> 3 mos after triptorelin start or pregnancy
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Triptorelin Plus Tamoxifen | Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline follicle-stimulating hormone (FSH) | 6 IU/L |
| Triptorelin Plus Tamoxifen | Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline luteinizing hormone (LH) | 6 IU/L |
| Triptorelin Plus Exemestane | Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline follicle-stimulating hormone (FSH) | 32 IU/L |
| Triptorelin Plus Exemestane | Baseline Endocrine Function Levels (FSH, LH) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline luteinizing hormone (LH) | 21 IU/L |
Secondary
Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm
The secondary analysis explored baseline estrogen levels (E2, E1, E1S) with suboptimal estrogen suppression (SES) where estrogen (E2) \> 2.72 pg/mL in the exemestane + triptorelin arm.
Time frame: Baseline
Population: All patients from the Intent to treat (ITT) population assigned to exemestane +triptorelin (N=83) according to suboptimal estrogen suppression (SES) with E2 \> 2.72 pg/mL (suboptimal threshold) or any vaginal bleeding \> 3 mos after triptorelin start or pregnancy
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Triptorelin Plus Tamoxifen | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estradiol (E2) | 80 pg/mL |
| Triptorelin Plus Tamoxifen | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estrone (E1) | 50 pg/mL |
| Triptorelin Plus Tamoxifen | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estrone sulphate (E1S) | 928 pg/mL |
| Triptorelin Plus Exemestane | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estradiol (E2) | 39 pg/mL |
| Triptorelin Plus Exemestane | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estrone (E1) | 41 pg/mL |
| Triptorelin Plus Exemestane | Baseline Estrogen Levels (E2, E1, E1S) With Suboptimal Estrogen Suppression (SES) in the Exemestane + Triptorelin Arm | Baseline estrone sulphate (E1S) | 715 pg/mL |
Secondary
Comparison of Estrogen Levels at Different Time Points During Treatment
Percent (%) change of estrogen levels estradiol (E2), estrone (E1), and estrone sulphate (E1S) at each timepoint from baseline: e.g. {E2(t)-E2(0)} / E2(0)\*100, where t= 3, 6, 12, 18, 24, 36, and 48 months from randomization
Time frame: baseline (0 months), 3, 6, 12, 18, 24, 36, and 48 months from randomization
Population: The final (4 years) analysis cohort (N=109) consists of all patients from the intent to treat (ITT) population (N=123) who had at least 2 samples analyzed and who received at least one GnRH analogue triptorelin injection during follow-up. Fourteen patients were excluded due to the reasons of 1) never start TE and never received GnRH (gonadotropin-releasing hormone) analogue triptorelin; 2) only baseline sample available; 3) single sample at 24 months; 4) patients without sample analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 18 months | -44 percent change of estrogen levels | Standard Deviation 37 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 12 months | -57 percent change of estrogen levels | Standard Deviation 61 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 24 months | -40 percent change of estrogen levels | Standard Deviation 43 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 48 months | -65 percent change of estrogen levels | Standard Deviation 41 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 36 months | -29 percent change of estrogen levels | Standard Deviation 39 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 48 months | -41 percent change of estrogen levels | Standard Deviation 33 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 18 months | -61 percent change of estrogen levels | Standard Deviation 50 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 3 months | -43 percent change of estrogen levels | Standard Deviation 73 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 3 months | -48 percent change of estrogen levels | Standard Deviation 41 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 6 months | -50 percent change of estrogen levels | Standard Deviation 59 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 6 months | -69 percent change of estrogen levels | Standard Deviation 44 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 12 months | -35 percent change of estrogen levels | Standard Deviation 82 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 6 months | -43 percent change of estrogen levels | Standard Deviation 50 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 18 months | -35 percent change of estrogen levels | Standard Deviation 68 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 24 months | -63 percent change of estrogen levels | Standard Deviation 48 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 24 months | -27 percent change of estrogen levels | Standard Deviation 87 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 12 months | -38 percent change of estrogen levels | Standard Deviation 55 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 36 months | -26 percent change of estrogen levels | Standard Deviation 63 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 3 months | -70 percent change of estrogen levels | Standard Deviation 40 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 48 months | -36 percent change of estrogen levels | Standard Deviation 66 |
| Triptorelin Plus Tamoxifen | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 36 months | -56 percent change of estrogen levels | Standard Deviation 44 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 48 months | -87 percent change of estrogen levels | Standard Deviation 53 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 3 months | -76 percent change of estrogen levels | Standard Deviation 75 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 6 months | -82 percent change of estrogen levels | Standard Deviation 62 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 12 months | -83 percent change of estrogen levels | Standard Deviation 47 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 18 months | -85 percent change of estrogen levels | Standard Deviation 37 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 24 months | -79 percent change of estrogen levels | Standard Deviation 61 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 36 months | -86 percent change of estrogen levels | Standard Deviation 33 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estradiol (E2) at 48 months | -79 percent change of estrogen levels | Standard Deviation 87 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 3 months | -90 percent change of estrogen levels | Standard Deviation 18 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 6 months | -90 percent change of estrogen levels | Standard Deviation 19 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 12 months | -81 percent change of estrogen levels | Standard Deviation 61 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 18 months | -75 percent change of estrogen levels | Standard Deviation 86 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 24 months | -84 percent change of estrogen levels | Standard Deviation 33 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 36 months | -82 percent change of estrogen levels | Standard Deviation 35 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone (E1) at 48 months | -70 percent change of estrogen levels | Standard Deviation 133 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 0 months (baseline) | 0 percent change of estrogen levels | Standard Deviation 0 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 3 months | -90 percent change of estrogen levels | Standard Deviation 27 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 6 months | -87 percent change of estrogen levels | Standard Deviation 35 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 12 months | -92 percent change of estrogen levels | Standard Deviation 17 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 18 months | -92 percent change of estrogen levels | Standard Deviation 16 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 24 months | -88 percent change of estrogen levels | Standard Deviation 33 |
| Triptorelin Plus Exemestane | Comparison of Estrogen Levels at Different Time Points During Treatment | Percent change from baseline of estrone sulfate (E1S) at 36 months | -70 percent change of estrogen levels | Standard Deviation 173 |
Secondary
Endocrine Functions (FSH and LH) Status According to Treatment Assignments
Endocrine function (FSH, LH) status according to treatment assignments at 12 months using 12 month data alone or 12 month data plus earlier data (when 12 month not available)
Time frame: Less than 12 months, at 12 months
Population: The final (4 years) analysis cohort (N=109) consists of all patients from the intent to treat (ITT) population (N=123) who had at least 2 samples analyzed and who received at least one GnRH analogue triptorelin injection during follow-up. Fourteen patients were excluded due to the reasons of 1) never start TE and never received GnRH (gonadotropin-releasing hormone) analogue triptorelin; 2) only baseline sample available; 3) single sample at 24 months; 4) patients without sample analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Triptorelin Plus Tamoxifen | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Follicle-stimulating hormone (FSH) at 12 months | 2.0 IU/L |
| Triptorelin Plus Tamoxifen | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Follicle-stimulating hormone (FSH) at <=12 months | 2.2 IU/L |
| Triptorelin Plus Tamoxifen | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Luteinizing hormone (LH) at 12 months | 0.2 IU/L |
| Triptorelin Plus Tamoxifen | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Luteinizing hormone (LH) at <=12 months | 0.2 IU/L |
| Triptorelin Plus Exemestane | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Luteinizing hormone (LH) at <=12 months | 0.1 IU/L |
| Triptorelin Plus Exemestane | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Follicle-stimulating hormone (FSH) at 12 months | 7.0 IU/L |
| Triptorelin Plus Exemestane | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Luteinizing hormone (LH) at 12 months | 0.1 IU/L |
| Triptorelin Plus Exemestane | Endocrine Functions (FSH and LH) Status According to Treatment Assignments | Follicle-stimulating hormone (FSH) at <=12 months | 6.5 IU/L |
Secondary
Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression
Potential predictive factors of ineffective estrogen suppression (SES) (with E2 \> 2.72 pg/mL, or any vaginal bleeding \> 3 months after triptorelin start or pregnancy) such as: age, evidence of menses at entry, BMI, chemotherapy (yes/no), and, type of chemotherapy received
Time frame: Four years after randomization
Population: All patients from the Intent to treat (ITT) population assigned to exemestane +triptorelin (N=83) according to suboptimal estrogen suppression (SES) with E2 \> 2.72 pg/mL (suboptimal threshold) or any vaginal bleeding \> 3 mos after triptorelin start or pregnancy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, irregular | 3 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), obese (>=30) | 3 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Age at randomization (years), <35 | 3 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo, no | 12 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, persistent amenorrhea | 5 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo, yes | 9 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, normal | 13 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), normal (<25) | 9 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, anthracycline-based | 3 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Age at randomization (years), >=35 | 18 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, taxane-based | 0 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), over weight (25-<30) | 8 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, anthracycline+taxane | 6 Participants |
| Triptorelin Plus Tamoxifen | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, no chemo | 12 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, anthracycline+taxane | 28 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Age at randomization (years), <35 | 5 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Age at randomization (years), >=35 | 57 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, normal | 24 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, irregular | 11 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Menstrual status, persistent amenorrhea | 27 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), normal (<25) | 36 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), over weight (25-<30) | 16 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | BMI (kg/m2), obese (>=30) | 9 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo, no | 25 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo, yes | 37 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, no chemo | 25 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, anthracycline-based | 7 Participants |
| Triptorelin Plus Exemestane | Number of Participants With Potential Predictive Factors of Ineffective Estrogen Suppression | Prior chemo regimen, taxane-based | 2 Participants |