Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression (NCT00944047), a na phase 2 study. The primary outcome is Pathologic Complete Response.

2. Clinical Question

The study asks whether a regimen including trastuzumab and chemotherapy before surgery is associated with pathologic complete response in invasive breast cancer described as having low HER2 expression. The registry record identifies the population as HER2 1+ or 2+ by immunohistochemistry in the official title. It does not report a comparator group, so the record does not support a direct treatment-versus-control comparison.

3. Trial Design

This is a phase 2, single-group study with an enrollment of 32. The registry lists the study as completed. Its recorded start is 2009-07 and its primary completion is 2014-05. The sponsor is the University of Kansas Medical Center.

The intervention arm description includes nab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, growth factor support, and surgery. The official title describes nab-paclitaxel and trastuzumab followed by dose-dense doxorubicin and cyclophosphamide as neoadjuvant therapy. The registry does not report dose schedules, treatment duration details beyond the primary outcome timeframe, or eligibility criteria beyond the disease and HER2 description stated in the title.

Allocation is recorded as NA, masking as none, and the model as single group. Those entries indicate that the record does not describe random assignment or a masked comparison. No separate control arm is listed. Consequently, any observed outcome in the intervention arm would describe participants receiving the study regimen; it would not, by itself, estimate how outcomes would have differed under a concurrent alternative treatment.

The registry identifies 1 primary outcome measure: pathologic complete response, measured as a percentage of participants at 22 weeks. Although the study is marked completed, the outcome result is not reported in the registry record. The record also lists 0 analyses. Details of the protocol’s statistical analysis plan, sample-size justification, interim analyses, and analysis populations are not reported in the registry record.

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

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 Pathologic Complete Response, measured over 22 weeks.

Pathologic complete response is the named primary endpoint. The registry expresses it as a percentage of participants and gives a timeframe of 22 weeks. In statistical terms, the endpoint is a binary outcome summarized as a proportion: participants are classified according to whether they meet the study’s definition of complete response, and that proportion is reported on a percentage scale.

The registry record does not specify the pathology criteria for response, the exact assessment procedures, or how the endpoint handles participants whose status cannot be assessed. Those details matter because they determine who counts in the numerator and denominator and how consistently the outcome can be measured. They are not reported in the registry record.

A pathologic response endpoint is used to describe tumor response assessed in relation to tissue pathology rather than relying only on a symptom or imaging measure. That is a general description of the endpoint concept; it does not fill in this study’s missing operational definition. The stated 22-week timeframe identifies when the registry associates the primary measure with assessment, but it does not provide an observed percentage or an estimate of uncertainty. The primary outcome result is not reported in the registry record, so the endpoint’s observed value cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical feature of this study is its single-group design. That design can describe outcomes among participants receiving the listed regimen, but it does not create a concurrent estimate of what would have happened to comparable participants under another treatment. In general, a control group helps distinguish an intervention-associated outcome from changes that may arise from the disease course, participant selection, other care, or measurement. Those issues cannot be resolved by a single-arm result alone.

How to understand a binary percentage

The primary endpoint is a percentage of participants with pathologic complete response. A binary endpoint has two possible classifications for each participant under the study definition: meeting or not meeting the response criterion. The reported percentage is a summary of the number meeting that criterion relative to a defined denominator. The registry names the endpoint but does not provide its operational criteria, denominator, or observed value.

For a binary percentage, uncertainty is usually expressed with a confidence interval. In general, a confidence interval describes the range of values reasonably compatible with the data under the method used; it is not a guarantee that the true value lies in that particular interval. Its width depends on the amount of information and the method of calculation. No confidence interval for pathologic complete response is reported in the registry record, so its precision cannot be evaluated.

Why the denominator matters

The denominator should correspond to a clearly stated analysis population. It may differ from the number enrolled if some participants do not receive treatment, do not reach assessment, or lack an evaluable result. These are general possibilities, not claims about what happened in this study. Although enrollment is 32, the registry does not report how many participants had an endpoint assessment or how many were included in an endpoint analysis. The endpoint denominator is therefore not reported in the registry record.

Missing endpoint status can affect a binary estimate. In general, excluding participants with missing data can change the composition of the analyzed group, while classifying missing outcomes as response or nonresponse imposes assumptions. More formal methods also depend on assumptions about why data are missing and how the missingness relates to observed information. The registry does not report the extent of missing endpoint data or the method used to handle it. No particular missing-data mechanism or approach should be inferred.

What the design can and cannot estimate

A single-group proportion estimates the observed frequency of the endpoint in the analyzed group. It is not, on its own, a randomized treatment effect. A treatment effect normally compares outcomes between groups or against an appropriate counterfactual. Because allocation is listed as NA and the model as single group, the record supplies no like-for-like control comparison. A change from an external or historical benchmark would require details about that benchmark and its comparability; such an analysis is not reported in the registry record.

General statistical tests and confidence intervals answer different questions. A test assesses compatibility with a stated null hypothesis under its assumptions, whereas an interval conveys the range and precision of an estimated quantity. Both depend on the chosen analysis and the data. The registry reports 0 analyses and does not state a hypothesis test, null value, confidence-interval method, or model for the primary outcome. No inferential result can be reconstructed from the posted registry information.

Planning illustrations are not observed power

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are described as planning calculations based on the observed effect, with the effect to detect set as a stated fraction of that effect. The illustrations assume two arms even though the registered study is single group. They should therefore be read as hypothetical design calculations, not as a description of the actual trial design or a comparison performed in this study.

Sample-size calculations describe how much information a hypothetical design might require under stated assumptions. They do not show the probability that this completed study detected an effect, and they are not observed power. In particular, planning calculations based on an observed effect do not replace a confidence interval or a prespecified design justification. The registry record does not report the trial’s own sample-size justification, and the primary outcome result needed to interpret an observed effect is not reported there.

Why over-dispersion is not the main issue

Over-dispersion is a general concern when observed variability exceeds what a chosen statistical model expects. It can matter in count or clustered data models, for example, because standard errors may then be too small if the extra variability is ignored. The registered primary measure is a percentage of participants with a binary outcome, and no model or analysis is reported. There is no basis in this record to assert that over-dispersion was assessed or that it affected the study’s results. More broadly, model assumptions can only be evaluated when the analysis and relevant data are available.

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("Intervention Arm")
n      <- c(32)
events <- c(8)
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  Intervention Arm  32  8  25.0  11.5  43.4  13.3  42.1  13.3  42.3

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 1 outcome measure and names pathologic complete response as the primary endpoint. It reports 0 analyses. No secondary outcome measures, multiple comparisons, subgroup analyses, or adjustment for multiplicity are described in the available record. Whether such analyses were planned or conducted is not reported in the registry record.

Multiplicity is a general issue that arises when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are considered, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that process. The record does not provide enough information to determine whether multiplicity was relevant to the study’s full protocol or whether any adjustment was used. It would be inappropriate to infer a strategy from the single primary outcome entry alone.

The registry does not describe the analysis population for the primary endpoint. It also does not report the number of participants with evaluable pathology at 22 weeks, the amount or pattern of missing endpoint information, or how missing outcomes were handled. These details affect the denominator and interpretation of a percentage. No specific analysis population, such as an intention-to-treat or per-protocol population, is reported in the registry record.

In general, missing-data methods rely on assumptions about the relationship between missingness and observed or unobserved outcomes. Sensitivity analyses can show how conclusions might vary under alternative assumptions, but the record does not report whether any were performed. The completed status and enrollment count do not resolve these reporting gaps. Consequently, neither the risk of selective analysis nor the robustness of the primary endpoint result can be assessed from the registry record.

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: febrile neutropenia (6.2%), pneumonia (3.1%), syncope (3.1%), pain (3.1%).

The registry lists 32 participants at risk for serious adverse events and 5 affected participants in the intervention arm. It separately lists 32 participants at risk for other adverse events and 32 affected. These are registry counts of participants, not a complete account of the number, duration, or clinical course of individual events. The record does not provide a safety comparison group.

The listed serious adverse event terms and percentages are febrile neutropenia at 6.2%, pneumonia at 3.1%, syncope at 3.1%, and pain at 3.1%. These are the terms and percentages recorded; the registry entry does not provide further detail about event timing, severity grades, duration, recurrence, or attribution to a particular treatment component. It also does not state whether the listed terms are mutually exclusive, so they should not be added together or interpreted as separate groups of participants.

The deaths field is null, so death information is not reported in the registry record. The record also does not state the follow-up period for the safety counts. These limitations mean that the entries can be read descriptively but not used to compare risks across treatments or to characterize safety comprehensively. They are separate from the unreported primary pathologic complete response result.

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

The registry record establishes that a phase 2, single-group study enrolled 32 participants with breast cancer and evaluated a neoadjuvant regimen that included nab-paclitaxel, trastuzumab, doxorubicin, and cyclophosphamide, with growth factor support and surgery. It identifies pathologic complete response as the primary outcome, expressed as a percentage of participants at 22 weeks.

What it does not establish is the observed response percentage. That result is not reported in the registry record, and neither a confidence interval nor a statistical test is listed. Without the endpoint estimate, its denominator, and an uncertainty measure, the magnitude and precision of the primary outcome cannot be assessed from this record. The completed status should not be mistaken for a posted efficacy result.

The single-group design also limits what any observed percentage could mean. A proportion in the treated group would describe outcomes in that group; it would not by itself quantify a causal difference from another treatment. There is no separate comparator arm in the registry entry, and no randomized comparison is described. The study’s objective refers to benefit from adding trastuzumab, but the registered design does not include a control arm that isolates trastuzumab’s contribution.

The safety entries provide counts of affected participants and selected serious adverse event terms, but without a concurrent comparator, detailed follow-up, or broader event data they do not establish relative safety. Likewise, the enrollment count does not show how many participants had an evaluable primary endpoint. The analysis population and missing-data handling are not reported in the registry record.

Accordingly, the appropriate reading is descriptive and limited: the record documents the intended clinical question, regimen, design, enrollment, timeframe, and selected safety entries, while leaving the primary outcome result and its statistical uncertainty unreported. It does not support a conclusion that the regimen did or did not produce a particular response or comparative benefit.

14. Why This Trial Matters Statistically

This study illustrates why clinical trial interpretation depends on both an outcome estimate and a design capable of answering the intended comparison. The registered question concerns adding trastuzumab to chemotherapy, but the record describes a single intervention group rather than a separate group receiving the same chemotherapy without trastuzumab. A response proportion from one group cannot isolate the contribution of one component of a multi-component regimen.

It also illustrates the distinction between a registered endpoint and a reported result. The record specifies pathologic complete response, a percentage scale, and a 22-week timeframe. Those details define the intended outcome at a high level, but an endpoint label alone does not show what was observed, how precisely it was estimated, or which participants contributed to the denominator. Here, the outcome result is not reported in the registry record.

The entry is also useful for demonstrating that completion status, enrollment, and analysis are distinct. The study is listed as completed with 32 enrolled participants, but the record lists 0 analyses and does not give the primary outcome estimate. Neither completion nor enrollment can substitute for an analysis result. Statistical interpretation requires the observed data summary and enough information to understand how it was produced.

Finally, this record highlights the importance of reporting definitions, analysis populations, missing-data handling, and uncertainty. Without those elements, readers cannot assess how robust a binary endpoint estimate would be or how precisely it represents the study group. These are general principles of evidence interpretation, and the missing details are especially consequential when the design lacks a concurrent comparator.

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 outcome result is not reported in the registry record. Although pathologic complete response is named as the primary endpoint and the timeframe is 22 weeks, there is no observed percentage, denominator, confidence interval, or statistical test result. The endpoint criteria and pathology assessment details are also not reported.

The single-group design does not provide a concurrent control for estimating a comparative treatment effect. The listed regimen combines several drugs with growth factor support and surgery, so this record cannot isolate the contribution of trastuzumab or any other individual component. Allocation is listed as NA and masking as none.

Enrollment was 32, but the record does not report how many participants were assessed for the primary endpoint or included in an analysis. The analysis population, missing-data extent, and missing-data approach are not reported in the registry record. This prevents assessment of the endpoint denominator and whether missing observations could affect interpretation.

The registry lists selected safety information but does not report the safety follow-up period, event-level details, attribution, or deaths. It also does not report the protocol’s sample-size justification, interim analyses, or detailed statistical plan. The planning illustrations use hypothetical two-arm assumptions and should not be treated as the design or analysis of this single-group study. These limitations concern the information available in the registry record and do not establish what may or may not appear in other study documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression — NCT00944047.
• Registry record last updated 2018-04-23; status last verified 2018-03.
• Results first posted 2018-04-23.
• 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 NCT00944047 as a completed phase 2, single-group study sponsored by the University of Kansas Medical Center. Enrollment was 32. The recorded start was 2009-07 and primary completion was 2014-05. The population is invasive breast cancer with low HER2 expression, described in the official title as 1+ or 2+ by IHC.

The intervention includes nab-paclitaxel, trastuzumab, doxorubicin, cyclophosphamide, growth factor support, and surgery. The primary outcome is pathologic complete response, expressed as a percentage of participants at 22 weeks. Its result and analysis are not reported in the registry record. Allocation is NA, masking is none, the model is single group, and the registry lists 0 analyses.

Safety entries list 5 participants affected by serious adverse events among 32 at risk and 32 affected by other adverse events among 32 at risk. Selected serious event terms and percentages are reported, while death information is not reported in the registry record.