Study of 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 24-02: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of 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 24-02 (NCT00975676), a randomized na study. The primary outcome is 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.

2. Clinical Question

The question concerns hormone measurements, not a clinical event such as recurrence or survival. The primary outcome names three estrogen measures and specifies their mean and standard deviation at baseline and at 3, 6, 12, 18, 24, 36, and 48 months after randomization. The stated purpose is to investigate estrogen suppression among women receiving triptorelin with either tamoxifen or exemestane. The registry also lists secondary outcomes concerning measurements over time, potential predictive factors of ineffective suppression, baseline hormone levels, and endocrine function.

The record describes a randomized study, but it does not report the numerical estrogen results or an inferential comparison between the treatment groups. Therefore, the clinical question can be stated from the registered outcome and treatment arms, but the registry record does not establish which regimen had lower measured levels or how uncertain any difference might be. It also does not report whether observed hormone levels were associated with later clinical outcomes.

3. Trial Design

The registry describes a randomized, parallel-group, unmasked substudy associated with IBCSG 24-02/SOFT. The enrollment is 123. The two arms are triptorelin plus tamoxifen and triptorelin plus exemestane. Arm descriptions refer to estrogen measurements from blood samples during treatment, while the primary outcome covers the first 4 years after randomization. The arm descriptions refer to treatment for 5 years; the stated primary outcome timeframe is shorter.

The study is listed with phase NA and has completed status. Its registered purpose is to examine estrogen levels in premenopausal women who had breast cancer surgery and were receiving triptorelin with tamoxifen or exemestane in the associated trial. The listed intervention for the substudy is gas chromatography / tandem mass spectometry. The record does not give further assay details or describe the randomization procedure, allocation concealment, or the number assigned to each arm.

The primary outcome analysis population is described as the final (4 years) analysis cohort. It consists of patients from the intent-to-treat population who had at least 2 samples analyzed and received at least one GnRH analogue triptorelin injection during follow-up. The record gives the cohort as N=109 and the intent-to-treat population as N=123. It says fourteen patients were excluded, but the detailed reasons are incomplete in the registry record; the available description begins a list of reasons but does not provide it in full.

The primary outcome lists measurements at 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization. The registry notes that some samples were not used, including unscheduled samples, samples taken after surgery or vaginal bleeding, and samples taken after early discontinuation or discontinuation of GnRH injections. It does not report the number of samples available at each time point or the resulting number of participants contributing to each measurement.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 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.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intent to treat (ITT) population: all patients receiving triptorelin plus either tamoxifen (T+Trip) or exemestane (E+Trip) with the exception of patients who withdrew consent and/or never started triptorelin. Analysis cohort (N=109): all patients from ITT population, who had two sample data were included, given the primary aims of this analysis is for the long term (4 years) data, patients with only baseline data were excluded. Fourteen patients were excluded.

6. Primary Endpoint

The registry lists the primary outcome as 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, measured over 0 (baseline), 3, 6, 12, 18, 24, 36, and 48 months after randomization.

The primary endpoint comprises estrogen levels—estradiol (E2), estrone (E1), and estrone sulphate (E1S)—measured in pg/mL. It is defined as a mean with standard deviation at baseline and at 3, 6, 12, 18, 24, 36, and 48 months after randomization. These are continuous laboratory measurements rather than counts of clinical events. The registry describes the measurements as being made during the first 4 years of treatment with triptorelin combined with either tamoxifen or exemestane.

As a general statistical rationale, repeated hormone measurements can describe the level and variability of a biomarker across follow-up. The mean gives a measure of the central level in the analyzed observations, while the standard deviation describes how spread out those observations are around the mean. Looking across scheduled time points can characterize the pattern of measured levels, provided the observations at each point and the handling of missing measurements are understood.

These measurements are relevant to the registered purpose of investigating estrogen suppression. They do not, on their own, measure recurrence, survival, symptoms, or another clinical outcome. The registry record does not report numerical endpoint values, confidence intervals, or a treatment-group contrast. It also does not report a threshold defining adequate suppression for the primary endpoint. Accordingly, the endpoint definition identifies what was to be measured but does not establish the magnitude, precision, or clinical implications of any observed group difference.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry specifies a continuous primary outcome summarized as a mean and standard deviation. It does not report the inferential method used to compare treatment groups or follow-up times. The explanations below distinguish the general meaning of the stated summaries from analysis details that are not reported in the registry record.

What does a mean describe?

In general, a mean is a measure of the center of a set of numerical observations. For a laboratory marker, it summarizes the measured levels among the observations included in that calculation. The mean alone does not show whether most measurements are near the center or whether a smaller number of unusually high or low values influence it. It also does not identify how many observations contributed unless that count is reported separately.

The registry names E2, E1, and E1S and gives pg/mL as the unit. Each measure can have its own distribution and its own pattern over time. A mean for one estrogen cannot be treated as a summary of the others. The registry does not provide the observed means or the underlying distributions, so the magnitude and shape of those measurements cannot be assessed from the record.

What does the standard deviation describe?

In general, a standard deviation describes the spread of observations around their mean. A larger standard deviation indicates more dispersion in the observed values, while a smaller one indicates that values are more concentrated around the mean. It is not the same as a confidence interval: the standard deviation describes variability among observations, whereas a confidence interval describes uncertainty in an estimated quantity under specified assumptions.

For a biomarker, variability may reflect differences between participants, variation within a participant over time, measurement variability, or a combination of these. A single standard deviation at a time point does not separate these sources. The registry reports the summary format but does not report values, confidence intervals, or the method used to account for the repeated observations from the same participant.

Why do the scheduled measurements matter?

The primary outcome is measured at baseline and at 3, 6, 12, 18, 24, 36, and 48 months after randomization. Repeated measurements can describe whether levels appear to change over follow-up and whether patterns differ between treatment groups. In general, observations from the same participant are correlated: a participant’s measurements over time are not necessarily independent of one another. Statistical methods for repeated measurements can account for that dependence, but the registry record does not state whether such a method was used.

Different approaches can answer different questions. A comparison at a particular follow-up point estimates a contrast at that point. A model using several time points may estimate an overall pattern or a treatment-by-time contrast. A change-from-baseline analysis focuses on within-participant change, while an analysis of follow-up levels may or may not adjust for baseline. These choices affect the estimand and interpretation. The analysis approach for this outcome is not reported in the registry record, so none of these approaches can be attributed to the study.

How should missing measurements be considered?

The outcome description states that some samples were not used. Examples include unscheduled samples, samples following surgery or vaginal bleeding, and samples taken after early discontinuation or discontinuation of GnRH injections. The analysis cohort also requires at least 2 analyzed samples and at least one triptorelin injection during follow-up. These rules define which observations or participants can contribute, but they do not explain how missing measurements were handled in an analysis.

In general, missing data can affect both the amount of information available and the interpretation of estimates. If missingness is related to participant characteristics, treatment, hormone levels, or events during follow-up, the analyzed observations may not represent all randomized participants in the same way. Whether this creates bias depends on the missingness process and the analysis assumptions. The registry record does not give time-point-specific missingness, reasons for each participant’s missing data, or a sensitivity analysis.

What is not reported about inference?

The record does not report a statistical model, a treatment-effect estimate, a confidence interval, a p-value, an interim-analysis plan, or a sample-size justification. It also does not state how the three estrogen measures and multiple time points were handled for multiplicity. Those details are needed to assess the planned or performed inferential comparisons. The number of analyses recorded is 0, so the registry record offers no inferential result to interpret.

In general, a p-value addresses compatibility between data and a specified null model; it does not measure the size or clinical importance of an effect. A confidence interval conveys uncertainty about an estimate, conditional on the method and assumptions. Neither can be reconstructed from the outcome description alone. The statistical interpretation is therefore limited to the endpoint definition, analysis-population description, and stated sample-exclusion rules.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 7 outcome measures, including the primary outcome and secondary outcomes concerning estrogen levels at different time points, potential predictive factors of ineffective estrogen suppression, baseline estrogen and endocrine function levels in the exemestane plus triptorelin arm, and endocrine-function status by treatment assignment. The primary outcome itself includes three estrogen measures and several follow-up points. The registry record does not report how multiplicity across outcomes, biomarkers, time points, or contrasts was addressed. It does not report an adjustment procedure, a hierarchy of tests, or a designated primary contrast within the repeated measurements.

As a general statistical matter, testing several related hypotheses can increase the chance of at least one apparently notable result arising by chance. Whether and how to control that risk depends on the objectives and analysis plan. Since no inferential analyses are reported, the record does not permit assessment of how multiplicity affected any findings.

Missingness is also relevant. The outcome description says that some samples were not used, including unscheduled samples and samples taken after surgery or vaginal bleeding, early discontinuation, or discontinuation of GnRH injections. The final analysis cohort is described as having at least 2 analyzed samples and at least one triptorelin injection during follow-up. The record gives the cohort and intent-to-treat population sizes, but does not report the number of missing measurements at each time point or by arm, or the methods used to handle them.

The analysis population is therefore not described as all randomized participants for the primary outcome. The detailed reasons for the stated exclusions are incomplete in the registry record, and no sensitivity analyses are reported. These omissions limit assessment of whether missing measurements or cohort selection could affect the estimates. The record also does not report whether all randomized participants were included in any secondary analysis population.

11. What the Result Does, and Does Not, Mean

The registry record describes a study intended to measure estrogen levels in women receiving triptorelin with tamoxifen or exemestane. It identifies the hormone measures, units, scheduled time points, treatment arms, and a final analysis cohort. Those details establish the scope of the registered question, but they are not numerical evidence about the observed estrogen levels.

No primary outcome values, treatment contrasts, uncertainty intervals, or inferential results are reported in the registry record. The available information therefore cannot establish whether one arm had higher or lower levels, whether levels changed over time, or how precisely any estimated pattern was measured. It cannot establish whether any observed difference would be clinically important.

Even if a difference in hormone measurements were reported, a biomarker result would not by itself demonstrate a difference in a clinical outcome. The primary endpoint concerns E2, E1, and E1S concentrations, not recurrence, survival, or another clinical event. The record does not report a link between these measurements and subsequent clinical outcomes. The stated purpose is to investigate estrogen suppression, but the outcome definition alone does not specify a threshold for adequate suppression.

Nor should zero values in the adverse-event fields be read as proof that no adverse events occurred. The fields for participants at risk are also zero, leaving no usable denominator for interpreting those counts. The adverse-event entries do not resolve the study’s hormone-level question.

The most defensible reading is that the registry documents a randomized, parallel substudy and its planned biomarker measurements, while leaving the numerical findings and their statistical interpretation unreported. Conclusions about direction, size, precision, safety, or clinical consequences cannot be drawn from the information in the registry record.

12. Why This Trial Matters Statistically

This study illustrates a statistical distinction between a clinical treatment question and a biomarker question. The registered primary outcome is based on repeated estrogen measurements, while the treatment combinations are described within a broader breast cancer trial. A hormone concentration can characterize a biological response, but it is not interchangeable with a clinical outcome. Keeping those endpoints distinct helps prevent conclusions about clinical benefit from being inferred solely from laboratory measurements.

The repeated-measure structure is also important. Measurements at baseline and across follow-up may provide information about patterns that a single measurement would not capture. At the same time, observations from the same participant are related, and measurements may be unavailable at some scheduled points. Statistical interpretation depends on how those features are handled. The registry record states the measurement schedule and several reasons samples were not used, but does not report the analysis model or missing-data approach.

The analysis-population description highlights another common issue: a randomized population and a biomarker analysis cohort need not be identical. Eligibility for the final cohort depends on analyzed samples and receipt of a triptorelin injection during follow-up. Clear reporting of participant flow, per-time-point observations, and the analysis approach would help readers assess how the resulting summaries relate to the randomized groups.

Finally, a registration record can define a research question without reporting results. Here, the outcome details are specific, but numerical summaries and inferential analyses are not reported. That distinction is useful when evaluating what a registry entry can support: it can explain what was intended to be measured, but it cannot substitute for estimates, uncertainty, and transparent analysis reporting.

13. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report numerical results for the primary estrogen outcomes. There are no arm-specific means or standard deviations, estimates of between-arm differences, confidence intervals, or p-values. The record reports 0 analyses, so there is no inferential result available to evaluate. This prevents assessment of the size, direction, and precision of any treatment contrast.

The outcome description gives several scheduled time points but does not report the number of measurements contributing at each point or in each arm. It also says that some samples were not used for specified reasons, including unscheduled collection, surgery or vaginal bleeding, and collection after early discontinuation or discontinuation of GnRH injections. The detailed reasons for the stated participant exclusions are incomplete in the registry record. Without fuller participant-flow and missingness information, the representativeness of the analyzed observations cannot be assessed.

The final analysis cohort is defined by sample availability and receipt of at least one triptorelin injection. This differs in definition from the intent-to-treat population. The record does not report how the analysis population was selected by treatment arm, whether all randomized participants were included in any analysis, or whether sensitivity analyses examined the effect of cohort selection.

The statistical model and the handling of repeated measurements are not reported. Neither are details of adjustment for baseline levels, treatment-by-time comparisons, multiplicity, or uncertainty estimation. The assay is named, but further laboratory methods and quality-control details are not reported in the registry record. Finally, the registry’s adverse-event fields have zero counts and zero at-risk entries, so they do not support a meaningful safety interpretation.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Study of 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 24-02 — NCT00975676.
• Registry record last updated 2021-10-25; status last verified 2021-09.
• Results first posted 2021-10-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

17. Record Summary

The record describes a completed, randomized, parallel, unmasked substudy in premenopausal women who had undergone breast cancer surgery. It compares triptorelin plus tamoxifen with triptorelin plus exemestane and lists enrollment of 123. The primary outcome is mean estradiol (E2), estrone (E1), and estrone sulphate (E1S), in pg/mL, measured from baseline through 48 months after randomization.

The final analysis cohort is described as N=109 from an intent-to-treat population of N=123, with inclusion requiring at least 2 analyzed samples and at least one triptorelin injection during follow-up. The record notes that some samples were not used and does not give complete exclusion details or time-point-specific sample counts.

Numerical primary outcome results and inferential analyses are not reported in the registry record. Consequently, the record defines the study question and measurement plan but does not establish the observed hormone levels or a comparative effect.