Anastrozole and Fulvestrant Compared to Anastrozole as Adjuvant Treatment of Postmenopausal Patients With Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anastrozole and Fulvestrant Compared to Anastrozole as Adjuvant Treatment of Postmenopausal Patients With Breast Cancer (NCT00357110), a randomized phase 2 study. The primary outcome is Patients Event-free at 12 Months (Where Event = Death (From Any Cause), Disseminated Tumour Cells (DTC) Positive at 12 Months or Clinical Disease Recurrence).

2. Clinical Question

The clinical question concerns whether the posted 12-month event-free counts differ between the combination arm and the anastrozole-only arm. The endpoint brings together events that reflect different aspects of disease status: death, a positive disseminated-tumour-cell finding, and clinical recurrence. A patient is counted as event-free only if none of the endpoint’s listed event conditions applies, according to the registry definition. The registry record does not provide a separate result for each component, so the posted count cannot show which component, if any, accounts for an event.

The record lists 6 event-free patients in the Fulvestrant + Anastrozole arm and 7 in the Anastrozole arm. These are counts, not an adjusted treatment-effect estimate. The registry does not report an inferential comparison or uncertainty interval for the contrast. The question the trial set out to address and the numerical description that can be read from the posted primary outcome should therefore be kept distinct: the trial was intended to compare treatment groups, while the available primary result is a count for each group.

3. Trial Design

NCT00357110 is a randomized phase II study with a parallel-group design. The registry lists no masking, so the study is recorded as unmasked. The two treatment groups were anastrozole monotherapy and anastrozole plus fulvestrant. The stated enrollment is 13. The record gives a start date of 2006-04 and a primary completion date of 2008-10, and the study status is completed. AstraZeneca is listed as the sponsor.

The official title describes adjuvant treatment of postmenopausal patients with early breast cancer and disseminated tumour cells in bone marrow. The study summary says the purpose was to compare the frequency of events after 1 and 2 years of adjuvant treatment. The posted primary outcome, however, is explicitly defined at 12 months following randomisation. No result for the 2-year time point is included among the posted outcomes described in the registry record.

The primary outcome is a count of patients event-free at 12 months. The combination arm has a listed arm size of 6 and a posted event-free count of 6; the anastrozole arm has a listed arm size of 7 and a posted event-free count of 7. These figures are best read as the registry’s descriptive outcome entries. They do not supply a treatment-effect estimate, confidence interval, or test of the between-arm difference.

The record lists one outcome measure and no posted analyses. It does not report the randomisation procedure, allocation concealment, the intended analysis population, or a detailed statistical analysis plan. Those details cannot be inferred from the randomized, parallel-group designation. Likewise, the record does not report the rationale for the enrollment target or a sample-size justification. The available information therefore establishes the broad design and the recorded outcome, but not the full conduct or analysis procedures.

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.

6. Primary Endpoint

The registry lists the primary outcome as Patients Event-free at 12 Months (Where Event = Death (From Any Cause), Disseminated Tumour Cells (DTC) Positive at 12 Months or Clinical Disease Recurrence), measured over 12 month period following randomisation.

The primary endpoint counts patients who were event-free during the 12 month period following randomisation. The registry defines an event as death from any cause, disseminated tumour cells positive at 12 months, or clinical disease recurrence. This is a composite endpoint: a patient is not event-free if any listed event condition applies. The posted measure is the number of event-free patients, rather than a time-to-event estimate or a separate count for each event component.

A composite can summarize more than one clinically relevant type of outcome in a single measure. In general, this can make an endpoint more inclusive, but interpretation depends on the components: they may differ in severity, frequency, and how they are assessed. The registry record does not provide component-specific results or additional details about how the disseminated tumour cell assessment and recurrence were determined. It is therefore not possible to tell from the posted primary count which component contributed to any non-event-free status.

The endpoint is useful for describing the study’s stated 12-month outcome, but it should not be read as a measure of long-term recurrence or survival. The brief study summary mentions event frequency after 1 and 2 years, while the posted primary result concerns 12 months. A result for the later time point is not reported in the registry record. The record also does not give a separately posted estimate of the probability of being event-free, an uncertainty interval, or a comparison adjusted for other factors.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is recorded?

The primary measure is binary at the participant level: for the 12-month endpoint, a patient is classified as event-free or not event-free according to the registry definition. The posted result is the number event-free in each arm. A binary outcome has two possible states for each participant, even though the registry reports the event-free count rather than a full participant-level dataset. The registry record does not provide separate counts for each component of the composite event.

In general, an analysis of a binary outcome can compare the event or event-free proportions between groups, or express the contrast using another effect measure. These approaches require clearly defined group denominators and an appropriate analysis population. The record lists arm sizes and outcome counts but does not provide an inferential estimate for this endpoint. No effect measure should be inferred from the descriptive counts in place of that unreported analysis.

Why is no two-arm comparison reported?

The registry record indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. This status means that a comparative estimate is not available in the posted results. It does not identify the reason. In particular, the record does not say whether the issue concerns the data structure, an analysis choice, missing information, or another matter. Those possibilities should not be treated as explanations of what happened in this trial.

When a sponsor reports an analysis, that analysis may include features that are not recoverable from aggregate counts alone. General examples include prespecified definitions, treatment of missing outcome status, covariate adjustment, or the method used to calculate uncertainty. None of those details is reported in the registry record for this result. The record lists no analyses, so there is no sponsor-reported treatment-effect estimate to interpret alongside the counts.

What does uncertainty add?

General statistical interpretation distinguishes an observed estimate from its uncertainty. A confidence interval describes uncertainty around an estimated effect under the assumptions of the chosen method. A p-value, when reported, evaluates compatibility with a specified null hypothesis under a statistical model; it does not measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.

With limited group sizes, estimates can be imprecise, but the degree of imprecision should be assessed from an uncertainty interval rather than inferred from the number of outcome entries alone. The registry does not give an interval for this endpoint. It is therefore not possible to determine from the posted record how broadly a comparative effect is compatible with the data. A lack of a reported statistical comparison is not the same as a finding of no difference.

How should planning calculations be understood?

The record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations, in general, estimate the number of participants per arm that a future study might require under stated assumptions. They are not a measure of power actually achieved in the completed trial, and they do not change the interpretation of the observed results.

The record also specifies that planning values for non-time-to-event outcomes would be expressed as participants per arm, while time-to-event illustrations would use a total number of events. The primary outcome in this record is a binary participant count, not a time-to-event endpoint. No numerical planning estimates are reported in the registry record. The assumed detectable effect is described relative to the observed effect, but the underlying effect estimate and the planning results are not available for interpretation. These assumptions should not be mistaken for a sample-size justification used to design the original trial: the original design rationale is not reported in the registry record.

What can and cannot be reconstructed?

Aggregate counts can describe what the registry records for each treatment group, but they do not disclose individual participant data or the analysis history. General considerations such as continuity corrections, exact tests, model choice, handling of incomplete outcomes, and adjustment for baseline variables can affect inferential results. The registry does not report which, if any, of these methods were planned or used. Since no comparative analysis is posted and the record explicitly marks the comparison as not estimable, a new test or interval should not be presented as though it were the trial’s reported analysis.

For this outcome, the defensible statistical reading is descriptive. The posted counts identify the number of event-free patients recorded for each arm. The record does not supply a comparative estimate, uncertainty measure, or analysis-population definition. Any stronger statistical conclusion would require information not reported in the registry 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("Fulvestrant + Anastrozole", "Anastrozole")
n      <- c(6, 7)
events <- c(6, 7)
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  Fulvestrant + Anastrozole  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Anastrozole  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no posted analyses. The primary outcome is the 12-month event-free count. The study summary mentions event frequencies after 1 and 2 years, but the registry’s posted outcome information does not include a result for the later time point. No secondary outcomes are posted. A multiplicity strategy for handling multiple endpoints or time points is not reported in the registry record, so it is not possible to determine whether any adjustment was planned or used.

Missing-data handling is also not reported in the registry record. The posted arm sizes and event-free counts do not describe whether all randomized patients had outcome status assessed, how any unavailable assessments were treated, or whether any participants were excluded from an analysis. The record does not identify an intention-to-treat population, a per-protocol population, or another analysis set. These omissions prevent an assessment of how the outcome data relate to the randomized population.

The record states that a two-arm comparison of the binary endpoint was not estimable because values were missing or not estimable for that comparison, but it does not explain the status. That statement should be reported as written rather than interpreted as proof of missing participant outcomes. The registry also does not report a detailed statistical analysis plan, interim analyses, or a sample-size justification. No inference about those procedures can be made from the posted counts.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: varicose vein (16.7%), goitre (14.3%), haemorrhoid operation (14.3%), sciatica (14.3%), renal failure (14.3%).

The registry lists serious adverse event information separately from the primary event-free outcome. In the Fulvestrant + Anastrozole group, 1 participant is listed as affected among 6 at risk for serious adverse events. In the Anastrozole group, 2 are listed as affected among 7 at risk. These are recorded counts. They are not a comparison adjusted for differences between groups, and the registry does not provide an uncertainty interval or inferential test for them.

The record lists Varicose Vein at 16.7%, and Goitre, Haemorrhoid Operation, Sciatica, and Renal Failure at 14.3% each among the top serious terms. The record does not provide further context for these term percentages in the posted information, including a group-specific breakdown. They should not be interpreted as comparative risks or as evidence that a particular treatment caused an event. The recorded death counts are not reported in the registry record.

In general, safety counts in a trial describe events observed and recorded under the study’s reporting definitions. A serious adverse event listing is distinct from the primary composite endpoint unless the endpoint definition explicitly includes that event. Here, the primary endpoint names death, disseminated tumour cells positive at 12 months, and clinical disease recurrence; the safety figures should be read as a separate set of registry entries.

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

The posted result establishes that the registry records 6 patients event-free at 12 months in the Fulvestrant + Anastrozole arm and 7 in the Anastrozole arm. It also records arm sizes of 6 and 7, respectively. These figures answer a descriptive question about the number of patients meeting the registry’s event-free definition. They do not provide a comparative treatment-effect estimate.

The result does not establish whether the treatment groups differ, whether they are equivalent, or how precise a possible difference might be. No confidence interval or p-value is reported for the primary comparison, and the registry marks the binary two-arm comparison as not estimable. A descriptive count should not be treated as a test of a hypothesis. The registry result also cannot identify which component of the composite endpoint is responsible for a patient not being counted as event-free, because component-specific results are not posted.

The endpoint is limited to the 12-month assessment following randomisation. Although the study summary describes evaluating event frequencies after 1 and 2 years, the posted primary measure is at 12 months and no 2-year result is reported in the registry record. The available result therefore does not describe longer-term outcomes. Nor does it provide information about outcomes outside the listed endpoint or about the separate contribution of death, tumour-cell status, and recurrence.

The completed randomized phase II design is relevant context, but it does not fill in analysis details that are absent from the registry. The record does not report how missing outcome data were handled, which analysis population was used, or a detailed statistical plan. Accordingly, the result should be read narrowly as the posted event-free counts and the record’s stated lack of an estimable comparison. It should not be used to make a clinical decision or to claim benefit or lack of benefit.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a posted outcome count and a complete comparative result. The registry gives an event-free count for each randomized arm, but does not provide an estimate of the treatment contrast or its uncertainty. A reader can identify what the record reports without treating those entries as a formal analysis.

The endpoint also illustrates the interpretive challenge of a composite outcome. Death, disseminated tumour cells positive at 12 months, and clinical disease recurrence are combined in the event definition. A single event-free count does not reveal the component-level pattern. That distinction matters because a composite can conceal variation among its parts; the record does not report component-specific counts that would allow a more detailed reading.

The study’s stated aim includes event frequency after 1 and 2 years, while the posted primary result is at 12 months. This underscores why the time point attached to an outcome needs to be read carefully. A result for a stated assessment period does not automatically answer questions about a later period, and the record does not report a later outcome result.

Finally, the record shows why transparency about analysis populations, missing data, and statistical methods matters. Without those details, descriptive counts can be reported accurately, but uncertainty and comparative inference remain unavailable. The registry’s notation that the two-arm comparison was not estimable is important context, not a basis for inventing a substitute analysis.

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 principal limitation of the posted statistical record is that it reports descriptive event-free counts but no comparative estimate, confidence interval, or p-value. The registry marks the binary two-arm comparison as not estimable and does not explain why. The reason is not reported in the registry record, so it cannot be resolved from the outcome entries alone.

The trial enrolled 13 participants, with listed arm sizes of 6 and 7. The record does not report a sample-size justification or design rationale for this enrollment. It also does not report an analysis population, the number with outcome status available, or how missing data were handled. Although the posted count in each arm matches its listed arm size, that fact alone does not establish the missing-data process or analysis set.

The endpoint is a composite, but the registry provides no component-specific outcome counts. It reports the primary outcome at 12 months; a result at the later time point mentioned in the study summary is not reported in the registry record. Assessment procedures, event adjudication, and the detailed timing or handling of outcome measurement are not reported in the registry record.

Additional design and analysis details are also absent, including the randomisation method, allocation concealment, a statistical analysis plan, and any multiplicity approach. No posted analyses are listed. These limitations constrain interpretation of the treatment comparison and its precision. They do not establish that the trial lacked these procedures; they indicate that the procedures are not described in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anastrozole and Fulvestrant Compared to Anastrozole as Adjuvant Treatment of Postmenopausal Patients With Breast Cancer — NCT00357110.
• Registry record last updated 2010-12-21; status last verified 2010-12.
• Results first posted 2010-01-22.
• 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

NCT00357110 is a completed randomized phase II parallel-group study sponsored by AstraZeneca. The registry lists no masking and an enrollment of 13. The study compared anastrozole plus fulvestrant with anastrozole alone as adjuvant treatment for postmenopausal patients with early breast cancer and disseminated tumour cells in bone marrow.

The posted primary outcome is the number of patients event-free at 12 months following randomisation. The registry records 6 event-free patients in the Fulvestrant + Anastrozole arm and 7 in the Anastrozole arm. The endpoint defines an event as death from any cause, disseminated tumour cells positive at 12 months, or clinical disease recurrence.

The registry lists one outcome measure and no posted analyses. It states that values are missing or not estimable for a two-arm binary comparison. No comparative effect estimate or uncertainty interval is reported. The study summary refers to event frequency after 1 and 2 years, but a later result is not reported in the registry record.