Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients (NCT00270894), a non-randomized phase 2 study. The primary outcome is Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule.

2. Clinical Question

The central question is about feasibility: whether participants could receive most of the planned treatment within the intended schedule. The primary endpoint is not a comparison of this regimen with another treatment, and the design does not estimate a treatment effect against a control group.

The registry also names pathologic response, clinical response before surgery, left ventricular ejection fraction, progression-free survival and overall survival as secondary outcomes. It lists seven outcome measures in total. Their definitions, measurement details and results are not reported in the registry record. The listed questions cover response, cardiac function and longer-term outcomes, but the record does not provide results with which to answer them.

The registry describes the study as a pilot trial and gives an enrollment of 30. That enrollment describes the study record; it does not by itself establish how many participants contributed to the primary endpoint. The endpoint result and its analysis population are not reported in the registry record.

3. Trial Design

This was a phase 2, non-randomized, single-group trial with no masking. It is marked completed in the registry. The recorded enrollment is 30. The study start is listed as 2005-11, and primary completion as 2011-08. The sponsor is Accelerated Community Oncology Research Network.

The study evaluated neoadjuvant treatment for HER2-positive stage II-III breast cancer. The regimen description lists epirubicin at 100 mg/m² and cyclophosphamide at 600 mg/m² every 2 weeks for 4 cycles, followed by a 3-week break. It then lists docetaxel at 75 mg/m² every 2 weeks for 4 cycles with trastuzumab. Trastuzumab is described as a 6 mg/kg loading dose once, followed by a 4 mg/kg maintenance dose. The brief summary describes the combination medicines as given every two weeks. Other treatment-delivery details are not reported in the registry record.

Because this is a single-group study, participants were not assigned to a concurrent control arm. The registry therefore does not support a like-for-like comparison of the regimen with another treatment. The absence of randomization and masking also means the design should be interpreted as a feasibility and outcome assessment within the treated group, not as a blinded randomized estimate of comparative efficacy.

The record does not report a sample-size justification, eligibility criteria beyond the described cancer type and stage, or further details of participant selection. It also does not state how treatment delays, dose reductions or discontinuations were handled in the primary endpoint analysis. Those omissions limit assessment of how the enrolled group and treatment delivery relate to the endpoint.

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.

Before assignment: Informed consent was obtained from all subjects, and all subjects underwent screening procedures to verify eligibility.

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 Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule, measured over From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks).

The primary endpoint is the percentage of participants able to complete more than 85% of the planned dose on schedule. The registry describes feasibility as completing the neoadjuvant portion on time with more than 85% of the protocol-specified dose. Its stated timeframe is from the start of treatment through the neoadjuvant treatment period, approximately 20 weeks.

This is a binary participant-level outcome: each participant either meets the stated completion criterion or does not, and the percentage summarizes the share meeting it among the participants included in the analysis. The endpoint combines dose delivery and timeliness. It is intended to describe whether the planned regimen could be delivered under the study conditions, rather than to measure tumor response or compare health outcomes between treatment groups.

For this percentage to be interpretable, the analysis needs a clear denominator and rules for classifying participants with missing treatment records, early discontinuation or incomplete follow-up. Those details, as well as the observed percentage and its uncertainty, are not reported in the registry record. The endpoint is therefore defined, but the posted record does not establish how often the criterion was met.

Feasibility outcomes can help characterize treatment delivery in a pilot study. They do not, by themselves, show whether a treatment improves clinical outcomes. In this trial, the primary endpoint addresses the ability to receive the intended dose on schedule; the named response and survival outcomes are separate questions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary endpoint expressed as a percentage. For each participant with an evaluable endpoint, the underlying classification concerns whether the stated dose-and-schedule threshold was met. The percentage is a summary of those classifications within an analysis population. Interpreting it requires knowing both the number meeting the criterion and the denominator used. Neither is reported in the registry record for this endpoint.

What does a percentage estimate?

A percentage is an estimate of the proportion of the analyzed group meeting a defined outcome. It is not a measure of how close an individual came to the threshold, and it does not describe the distribution of dose delays or reductions. Here, the criterion combines completion of more than 85% of the protocol-specified dose with being on schedule. The registry does not report separate results for dose completion and timing, nor does it specify how borderline or incomplete records were classified.

General statistical interpretation: an estimate based on a limited group has sampling uncertainty. A confidence interval expresses a range of values compatible with the observed data under the method's assumptions; it is not a guarantee that the true value lies within that range. The registry does not report a confidence interval for the primary endpoint, and without the endpoint count and denominator no interval can be reconstructed from the posted record.

Why do denominator rules matter?

The denominator might be all enrolled participants or a defined subset with sufficient treatment and follow-up information. The registry record does not state which analysis population was used. This matters because excluding participants with missing records or early treatment discontinuation can change the estimated percentage. A transparent analysis would define eligibility for the endpoint, explain how missing information was handled and report the number analyzed alongside the result. Those details are not reported in the registry record.

General statistical explanation: missingness can be informative. If missing endpoint records are related to treatment delays, toxicity or clinical status, analyzing only participants with complete records may give a distorted picture of feasibility. This is a general concern, not a claim about what happened in this trial. The posted record does not describe missing-data methods or participant flow for this endpoint.

What can a single-group design estimate?

A single-group study can describe outcomes among participants treated under its study conditions. Without a concurrent control group, it cannot directly estimate a randomized between-group contrast. The non-randomized allocation and absence of masking also leave no basis for treating the study as a blinded comparative trial. These are features of the design, not evidence that the study endpoint was or was not achieved.

General statistical explanation: a comparison with an external or historical benchmark would require an explicitly defined benchmark and assumptions about comparability. No such comparator or benchmark is reported in the registry record. The primary endpoint should therefore be read as a planned feasibility measure, not as an estimate of relative benefit.

How should planning calculations be read?

The registry's stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and effects defined as fractions of an observed effect. Those are assumptions for a planning illustration, not the design of this single-group trial. The record does not report the illustration's numerical outputs or the observed effect used as its reference. Any planning sample size is hypothetical and is not observed power. It should not be read as a result from the enrolled participants or as proof that the study was adequately powered for its endpoint.

General statistical explanation: sample-size planning asks how much information a future study might need under specified assumptions. It does not measure the probability that a completed study's result is true, and it cannot replace reporting the observed estimate and its uncertainty. Where an observed effect is used as a planning reference, the calculation depends on that effect and on the planning assumptions. The registry record does not provide the primary endpoint result needed to assess such a reference for this trial.

What is reported about analyses?

The record lists no analyses. It does not report a statistical analysis plan, an inferential test for the primary endpoint, adjustment for covariates, interim analyses or a rationale for the enrolled sample size. These matters are not reported in the registry record. Their absence prevents assessment of whether the endpoint was analyzed as planned or whether any prespecified analysis choices were followed.

General statistical explanation: a clear analysis plan helps distinguish prespecified questions from analyses selected after outcomes are known. It should identify the analysis population, endpoint definition, missing-data handling and methods for uncertainty or hypothesis testing. These principles explain what would support interpretation; they do not establish which methods this trial used. In the absence of reported analyses and endpoint results, no inferential conclusion can be drawn from 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("Neoadjuvant Therapy")
n      <- c(30)
events <- c(18)
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  Neoadjuvant Therapy  30  18  60.0  40.6  77.3  42.3  75.4  42.2  75.5

11. Multiplicity, Missing Data and Analysis Populations

The registry names five secondary outcomes: pathologic response, clinical response prior to surgery, left ventricular ejection fraction, progression-free survival and overall survival. It also lists seven outcome measures overall. The record does not give the full set of measure definitions or explain the relationship between the named outcomes and the total count.

When a study examines multiple outcomes, the chance of finding at least one apparently notable result can depend on how many analyses are performed and how they are interpreted. General statistical practice may address this through a prespecified hierarchy, adjustment procedure or careful emphasis on estimation rather than isolated tests. The registry record does not report a multiplicity strategy, and it lists no analyses. The secondary outcomes therefore cannot be interpreted as a set of confirmatory tests from the available record.

The endpoint analysis population and missing-data methods are also not reported in the registry record. There is no posted participant flow for the primary endpoint, no stated rule for handling participants who stop treatment or lack endpoint information, and no reported account of missing secondary outcome measurements. These omissions matter because the denominator and classification rules can affect a percentage, while missing follow-up can affect interpretation of response and time-to-event outcomes.

The record does not report whether an intention-to-treat, per-protocol or other analysis population was used. It also does not report a statistical analysis plan or interim analyses. These items should not be inferred from the trial's phase, completion status or planned outcomes.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (3.3%), congestive heart failure (3.3%), medical error (3.3%), interstitial lung disease (3.3%).

For the neoadjuvant therapy group, the registry lists 30 at risk for serious adverse events and 4 affected. It lists 30 at risk for other adverse events and 30 affected. These are the posted counts; the record does not provide additional details about the analysis population, observation period or event-level accounting.

The serious adverse-event terms listed most prominently are pneumonia, congestive heart failure, medical error and interstitial lung disease, each reported as 3.3%. The percentages are reproduced as recorded and are not recalculated. The record does not clarify whether a participant could contribute to more than one term, so the term-specific percentages should not be added or treated as mutually exclusive categories.

The registry's deaths field contains no reported value. It is therefore not possible to determine a death count from this record. The adverse-event listing also does not, by itself, establish that an event was caused by treatment. Timing, duration, severity grading beyond the serious-event classification and relatedness assessments are not reported in the registry record.

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

The posted record establishes that a phase 2 pilot study evaluated a sequential neoadjuvant regimen in HER2-positive stage II-III breast cancer and defined a primary feasibility endpoint. It also records enrollment, study design features and selected adverse-event counts. It does not report the observed primary endpoint result.

That absence is important. Without the number of participants meeting the dose-and-schedule criterion and the denominator analyzed, the registry cannot show how often the feasibility threshold was reached. Without an uncertainty estimate, the precision of such a result also cannot be assessed. The named secondary outcomes likewise have no results in the registry record.

The design sets further limits on interpretation. Because the study was single-group and non-randomized, it does not provide a concurrent control comparison. A result from this design, if reported, would describe outcomes in the treated study group; it would not by itself establish how outcomes compare with another treatment or what caused them. The absence of masking is another design feature to consider when evaluating outcomes that may involve judgment or assessment.

The safety counts should be read as registry entries, not as a complete account of treatment-related risk. The record gives counts for serious and other adverse events, plus selected serious-event terms, but does not report the full context needed to assess timing, follow-up or causal attribution. The death count is not reported in the registry record.

Accordingly, the available record supports a description of the study question and design, but not a conclusion about whether the primary feasibility criterion was met or about the clinical outcomes named as secondary measures. No treatment recommendation or comparative claim follows from the information recorded.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between treatment feasibility and treatment effect. Its primary endpoint concerns the ability to complete a planned dose on schedule. That can describe how treatment was delivered in the study, but it is not the same as measuring comparative clinical benefit. Keeping those questions separate is essential when reading a pilot study.

The design also illustrates why the comparison structure matters. A single-group, non-randomized study can characterize outcomes in its participants, but it does not create a randomized control contrast. Any interpretation must stay within that design. The record's completed status and enrollment figure do not change the kinds of questions the design can answer.

For the endpoint to be useful to readers, a report needs more than the threshold definition. The observed percentage, denominator, analysis population and uncertainty would show both the estimated feasibility and its precision. Clear reporting of missing treatment records and endpoint classification would help readers judge whether the estimate represents the enrolled group as intended. These elements are absent from the registry record.

The record also demonstrates the importance of distinguishing study outcomes from statistical analyses. Several secondary outcomes are named, but the registry lists no analyses and reports no results for them. A list of outcomes identifies planned questions; it does not provide evidence about their answers. Likewise, planning assumptions are not observed findings or observed power.

These distinctions make the registry informative about design while leaving the central result unresolved. The trial's statistical value cannot be judged from a feasibility result that is not posted, and the available safety counts cannot fill that gap.

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 main limitation for interpretation is that the primary endpoint result is not reported in the registry record. The number meeting the completion criterion, the denominator analyzed and an estimate of precision are all absent. The record therefore does not permit a direct assessment of the stated feasibility question.

The single-group, non-randomized design offers no concurrent control comparison. The record also specifies no masking. These design features limit comparative interpretation, particularly for outcomes that could be affected by participant or assessor expectations. They do not establish that any particular result was biased, but they constrain what a result could support.

Information needed to evaluate endpoint construction is missing. The registry does not report analysis-population rules, missing-data handling or how treatment discontinuation and incomplete records were classified for the primary endpoint. It does not provide participant flow or a statistical analysis plan. A sample-size justification and interim-analysis details are also not reported in the registry record.

Although several secondary outcomes are named, their results and analysis methods are absent. The record lists seven outcome measures overall but names five secondary outcomes, without explaining the remaining measures. It does not report a multiplicity approach. The adverse-event record gives selected counts and terms, but does not report event timing, duration, causal attribution or a death count. These omissions restrict both efficacy and safety interpretation.

The registry's arm description gives the listed drug doses and some sequence details, but does not report every treatment-delivery detail. The record should therefore not be treated as a complete protocol or a complete statistical report.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Chemotherapy + Herceptin in HER2 Positive Stage II-III Breast Cancer Patients — NCT00270894.
• Registry record last updated 2012-03-20; status last verified 2012-03.
• Results first posted 2012-03-12.
• 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 record describes a completed phase 2 pilot trial of sequential neoadjuvant chemotherapy plus trastuzumab for HER2-positive stage II-III breast cancer. It was non-randomized, unmasked and single-group, with an enrollment of 30. The primary endpoint was the percentage of participants completing more than 85% of the planned dose on schedule during the neoadjuvant period, stated as approximately 20 weeks.

The record names response, cardiac function and survival outcomes, and includes selected serious and other adverse-event counts. However, it does not report the primary endpoint result, secondary outcome results, analysis populations, missing-data methods or statistical analyses. The available information describes the study design and questions, but does not answer the primary feasibility question or support a comparative treatment conclusion.