Pre-Operative Window of Adjuvant Endocrine Therapy to Inform RT Decisions in Older Women With Early-Stage Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pre-Operative Window of Adjuvant Endocrine Therapy to Inform RT Decisions in Older Women With Early-Stage Breast Cancer (NCT04272801), a na phase 2 study. The primary outcome is Number of Participants Who Changed Their Preference for Adjuvant Radiation Treatment.

2. Clinical Question

3. Trial Design

The registry describes a prospective, multisite, exploratory phase 2 study with a single group. The listed allocation is not applicable, masking is none, and the model is single group. All enrolled participants are assigned to receive pre-operative endocrine therapy; the registry does not describe a concurrent control arm or random assignment. The choice and dose of endocrine therapy are at the discretion of the treating medical oncologist, with tamoxifen and aromatase inhibitors listed as options.

The study concerns whether a period of endocrine therapy before surgery can inform decisions about adjuvant treatment, including radiation after breast-conserving surgery. Its primary outcome focuses on whether participants change their preference for adjuvant radiation treatment. The registry also describes surveys addressing health-related quality of life, general symptom burden, illness perceptions, beliefs about medicine, perceived sensitivity to medicine, breast cancer beliefs, treatment decisions, and perceptions related to medical choices. These measures are described as relevant to adherence and decisions about adjuvant therapy after breast-conserving surgery.

The registry lists enrollment of 84 and a start date of 2020-04-07. It lists primary completion as 2024-06-05 and the status as active, not recruiting. Those are registry entries, not evidence that results have been posted or that every enrolled participant completed each assessment. The actual number analyzed for any outcome, participant flow, and follow-up completeness are not reported in the registry record.

Because the design is single group, changes in preference can be described among participants, but the study design alone cannot establish what would have happened to comparable participants without the pre-operative therapy. The registry record does not report a protocol-level statistical analysis plan, a sample-size justification, or details of interim analyses.

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:

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: A total of 84 participants consented. One was found ineligible after consent, leaving 83 as the baseline. Of these, 4 withdrew and 4 were lost to follow-up. Data from 75 participants were analyzed for baseline characteristics.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Changed Their Preference for Adjuvant Radiation Treatment, measured over up to 6 months.

The primary endpoint is the number of participants who changed their preference for adjuvant radiation treatment. It is defined through a change in a participant’s response to a question about that preference, with a stated timeframe of up to six months. This is a participant-level count: the target is how many people meet the definition of a changed response, rather than the size of a clinical measurement on a continuous scale.

Preference is relevant to this study because the stated aim is to use the pre-operative period to inform decisions about subsequent treatment. Survey responses can capture a participant’s stated view at different assessment points. A change in response can therefore describe whether preferences differ over the assessment period. It does not, by itself, explain why a preference changed, establish that the change was caused by endocrine therapy, or show what treatment decision was ultimately made.

The registry record does not report the specific assessment schedule, the exact wording and scoring rules for the preference question, or the number of participants whose preference changed. It also does not report a statistical estimate, confidence interval, or analysis result for this endpoint. Without those results, the endpoint’s observed frequency and precision cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a prospective, multisite, exploratory phase 2 study in a single group. Allocation is listed as not applicable, masking as none, and the model as single group. These design features set boundaries on the statistical questions that can be answered. In particular, without a randomized control group, analyses can describe outcomes within the enrolled participants but cannot provide a randomized estimate of what the outcome would have been under a different treatment strategy.

What does a participant count represent?

The primary outcome is a count of participants who changed their preference for adjuvant radiation treatment. The outcome is binary at the participant level: each participant either meets the registry’s change definition or does not, assuming the required responses are available. A count is not the same as a rate or proportion. To interpret a rate, readers also need to know the denominator—the number of participants with data eligible for the endpoint. The registry record does not report the primary count or its analysis denominator.

The endpoint definition refers to a change in response to a question, but the registry does not report the exact question, the response options, the assessments used to determine change, or how incomplete or inconsistent responses are classified. Those details matter because the operational definition determines which participants count as having changed their preference. They are not reported in the registry record.

What would an uncertainty interval tell readers?

General statistical explanation: a confidence interval gives a range of values compatible with an estimate under the assumptions of the statistical method. It conveys precision, not certainty that the true value lies within a particular realized interval. For a binary outcome, the interval is interpreted alongside the estimated count or proportion and the denominator. No estimate, denominator, or confidence interval for the primary endpoint is reported in the registry record. Thus, the precision of the endpoint cannot be assessed from the posted results.

A p-value, when available, addresses compatibility between data and a specified statistical model or null hypothesis; it does not express the probability that a hypothesis is true or measure the clinical importance of an effect. No primary analysis or p-value is reported in the registry record. The record also does not report a prespecified hypothesis, a decision threshold, or an analysis method for the primary endpoint. Statistical significance should therefore not be inferred.

How does the design affect interpretation?

In a single-group study, a before-and-after comparison can describe change among participants who have measurements at both assessments. General statistical explanation: paired measurements account for the fact that two observations from the same person are related. However, a paired comparison does not remove the influence of time, concurrent care, measurement effects, or other events. A control group can help address some alternative explanations, especially when participants are randomized, but this registry describes no such group. The record does not report whether the primary endpoint analysis uses paired responses or another approach.

The registry lists numerous survey outcomes related to quality of life, symptoms, beliefs, perceptions, treatment decisions, and adherence. When many outcomes or comparisons are examined, the chance of finding at least one apparently notable result can increase. General statistical explanation: multiplicity procedures can control or describe that risk, but the choice depends on which outcomes were prespecified and how they are related. The registry lists 11 outcome measures and zero analyses. It does not report a multiplicity strategy, a hierarchy of outcomes, or which measures were treated as primary versus exploratory beyond the named primary endpoint.

What can the planning calculations establish?

The registry record distinguishes planning illustrations from the study’s design. The illustrations are described as using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. They are not the study’s own design assumptions, and their sample sizes are planning illustrations, not observed power. This trial is single group, so an equal-allocation two-arm illustration does not describe its actual allocation. The registry record does not report a sample-size justification for the trial, and the posted results do not report a primary effect estimate from which readers could assess the basis for such planning values.

General statistical explanation: power is a design property tied to assumptions about an effect, variability, significance level, and sample size. It is not a measure of whether an observed study result is reliable. Retrospective calculations using an observed effect are especially difficult to interpret as evidence, because the observed effect is itself uncertain. A planning calculation cannot substitute for a confidence interval around a study estimate or for the results of a prespecified analysis.

Why do missing-data details matter?

Survey outcomes can be unavailable for participants who miss assessments or do not answer a question. An analysis limited to participants with complete responses may describe a subset whose experience differs from that of participants with missing data. General statistical explanation: methods for handling missing data rely on assumptions, and different assumptions can lead to different estimates. The registry record does not report the amount or pattern of missing primary-outcome data, any imputation method, or sensitivity analyses. The endpoint’s analysis population and the effect of missingness therefore cannot be evaluated from the record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Pre-operative endocrine therapy")
n      <- c(75)
events <- c(21)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Pre-operative endocrine therapy  75  21  28.0  18.2  39.6  19.1  39.0  19.1  39.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary participant count and secondary survey outcomes concerning quality of life, symptoms, beliefs, perceptions, treatment decisions, and adherence. It records zero analyses. The record does not report which secondary outcomes were analyzed, whether the outcomes were ordered by priority, or whether any multiplicity adjustment or other strategy was used to account for examining multiple outcomes. Without analysis results and a stated strategy, readers cannot assess whether any reported statistical findings would be exploratory or confirmatory. The registry does not report such findings.

Missing-data information is also absent. The record does not report how many participants completed the primary preference assessment, how many had responses at each assessment point, or how incomplete survey responses were handled. It does not describe whether analysis included all enrolled participants, only participants with complete data, or another defined group. These details affect interpretation because the number and characteristics of participants contributing data can differ from the enrollment total.

The registry record does not report imputation, sensitivity analyses, or assumptions about why data might be missing. General statistical context: a missing-data method cannot guarantee an unbiased answer unless its assumptions are suitable for the data. If survey response availability is related to treatment experience or preference, an analysis restricted to available responses could yield a different picture from one that accounts for missing responses. Since the pattern and handling of missing data are not reported in the registry record, the possible impact cannot be judged.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (1.3%), acute stroke (1.3%).

The posted safety figures list one group, pre-operative endocrine therapy, with 75 participants at risk. The record lists 2 participants affected by serious adverse events, 35 affected by other adverse events, and 0 deaths. Pulmonary Embolism and Acute Stroke are each listed among the most frequent serious terms, at 1.3% each. These entries describe the safety figures reported for the group; they do not provide a comparison with an untreated or randomized control group.

General statistical context: an event count describes how many events or participants were recorded according to the registry’s reporting method, while a percentage gives a frequency relative to some denominator. The record does not state the denominator or calculation details for the listed term percentages in the safety summary, so those percentages should be read as registry-reported figures rather than recalculated values. It also does not establish whether a participant could contribute more than one event or term.

Serious adverse events are not automatically evidence that treatment caused an event. Causal attribution requires clinical and study information beyond a count or term listing. The registry record does not report a comparator-based safety analysis or a causal assessment for these entries. The listed figures should therefore be interpreted as descriptive safety reporting, not as a causal estimate of treatment risk.

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

The study is designed to describe whether participants change their preference for adjuvant radiation treatment after a period of pre-operative endocrine therapy. That question connects survey responses to treatment decision-making, and the registry also lists patient-reported measures intended to assess quality of life, symptoms, illness perceptions, beliefs, and other factors related to adherence and decisions after breast-conserving surgery.

The registry record does not report the primary endpoint result, any statistical analysis, or the number of participants with usable responses. It therefore does not establish how often preferences changed or how precisely any change was estimated. The enrollment entry of 84 is not a substitute for an endpoint count or analysis denominator. Nor does the record provide evidence about whether any change in preference led to a particular adjuvant treatment decision.

Even if a change count were available, a single-group design would support a descriptive account of participants’ responses, not a randomized comparison of treatment strategies. It could not by itself establish that pre-operative endocrine therapy caused a preference change. Other experiences during care and the passage of time could also contribute, and the registry does not report methods that separate those influences.

The study’s listed safety figures describe adverse event reporting in the treatment group, but do not establish causation or comparative risk. The record also does not report the missing-data handling or analysis populations needed to assess how representative the observed survey responses might be. The sound conclusion is therefore limited: the registry describes an exploratory single-group study and a relevant preference endpoint, but does not post the endpoint findings needed to judge the observed result.

14. Why This Trial Matters Statistically

Statistically, this study addresses a question that is not captured by a clinical measurement alone: whether participants’ stated preferences about adjuvant radiation treatment change during a pre-operative period. Patient-reported outcomes can make preferences, symptoms, beliefs, and treatment perceptions explicit objects of study. These outcomes may help describe decision processes, provided their definitions, assessment schedules, and analysis methods are clear.

The study also illustrates why design and endpoint interpretation need to be considered together. A within-participant change can be informative as a description of how responses evolve, while the single-group design limits causal conclusions about why they evolve. A randomized comparator could address a different question, but the registry describes an exploratory single-group study rather than a comparative trial. Its findings, if posted, would need to be interpreted in the context of that design.

Transparent reporting of endpoint denominators, missing responses, assessment timing, and analysis methods is particularly important for survey outcomes. Those details help distinguish a change in preference among participants with complete responses from a pattern that might apply to the full enrolled group. The registry record does not report those details or the primary analysis result, so the statistical contribution cannot yet be judged from the posted record.

Finally, listing multiple patient-reported outcomes raises the importance of clearly identifying which questions are primary and how secondary analyses are treated. The registry names a primary preference endpoint and several secondary outcomes, but does not report analyses or a multiplicity approach. This makes the registered research question understandable while leaving the evidential strength of any outcome findings unavailable for assessment.

15. 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 the primary endpoint count, its denominator, an estimate of uncertainty, or a statistical analysis. It also does not report the exact wording of the preference question, the response categories, the timing of each assessment, or the operational rule for defining a change. Without these details, readers cannot independently assess how the endpoint was measured or how consistently it could be classified.

The single-group design has no randomized control condition. Any observed change in preference would be descriptive and could not isolate an effect of pre-operative endocrine therapy from other influences. Treatment choice and dose are determined by the treating medical oncologist, rather than assigned by a comparative randomization procedure. The registry record does not report how variation in treatment choices was handled analytically.

Although the record lists planned enrollment of 84, it does not report actual enrollment for the endpoint analysis, participant flow, survey completion, or reasons for missing responses. It does not identify the analysis population or describe missing-data methods. These omissions prevent assessment of whether the analyzed participants represent everyone enrolled.

The record lists 11 outcome measures but no analyses, and does not report a statistical plan, multiplicity strategy, sample-size justification, or interim analyses. The stated planning illustrations use assumptions for a hypothetical two-arm comparison that differ from the single-group study design; they should not be mistaken for the trial’s own design justification. These limitations concern what can be evaluated from the registry record and do not determine what analyses may have been conducted outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pre-Operative Window of Adjuvant Endocrine Therapy to Inform RT Decisions in Older Women With Early-Stage Breast Cancer — NCT04272801.
• Registry record last updated 2025-10-22; status last verified 2025-09.
• Results first posted 2025-10-22.
• 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.

19. Record Summary

The registry describes a prospective, multisite, exploratory phase 2 single-group study of pre-operative endocrine therapy in women aged 65 years or older with early-stage estrogen receptor-positive breast cancer. All participants are to receive three months of therapy, with treatment choice and dose at the treating medical oncologist’s discretion. The listed enrollment is 84.

The primary outcome is the number of participants who change their preference for adjuvant radiation treatment, assessed up to six months. The registry also lists survey-based secondary outcomes concerning quality of life, symptoms, beliefs, perceptions, adherence, and treatment decisions. The record lists 11 outcome measures and zero analyses.

The registry status is active, not recruiting; the listed primary completion date is 2024-06-05. The primary outcome result, analysis population, missing-data handling, and statistical analysis methods are not reported in the registry record. Safety entries list 75 participants at risk, 2 with serious adverse events, 35 with other adverse events, and 0 deaths.